a.) Manuel derivation of the Pelle system
1.) Data acquisition and analysis of the contained information
search in medline with 'phosphorylates and drosophila' (1995-1998)
--> 25 articles
query in AbXtract - http://columba.ebi.ac.uk:8765/~andrade/abx/
--> serine appears high
look for papers about serine kinases, this paper was interesting:
genetic studies have identified three intracellular components whose
activity is required for activation of dl
toll, a transmembrane receptor
pelle, a serine threonine protein kinase
and tube, a protein of unknown function
do they exist as such in the interactive fly?
Look at:
http://sdb.bio.purdue.edu/fly/aimain/1aahome.htm
pelle is there:
http://sdb.bio.purdue.edu/fly/torstoll/pelle.htm
Read the text and get the interactions described there on Pelle:
BIOLOGICAL OVERVIEW
"The message that Pelle transduces, the activation of the Toll receptor
by its ligand Spätzle, is passed to Cactus causing its
degradation. Freeing the Rel-related protein Dorsal from it
cytoplasmic inhibitor Cactus, allows Dorsal to translocate into
ventral and ventrolateral nuclei and direct gene expression."
So: pelle interacts either with Toll receptor or with Spätzle.
That's not clear from this text.
"it can be shown that a motif in Cactus, resembling the sites of
signal-dependent phosphorylation in the vertebrate Cactus homolog
IkappaB is essential for Pelle-induced Cactus degradation."
So: Cactus activates pelle
"The Pelle kinase appears to require Tube for its activation. Tube
protein associates with the membrane of the oocyte and is required to
pass the activation signal from the receptor Toll to Pelle. In the
process Tube also becomes phosphorylated by Pelle."
So: Pelle phosphorylates Tube.
"Whether Pelle can phosphorylate Cactus or Dorsal is unknown. Tube is
the one known target for Pelle phosphorylation"
Search again in MEDLINE. This time whith "pelle and drosophila" (no year limit)
22 articles!
Run them in AbXtract - http://columba.ebi.ac.uk:8765/~andrade/abx/
Search for sentences containing pelle and describing interactions:
functional interactions between the pelle kinase, toll receptor, and
tube suggest a mechanism for activation of dorsal a complex signal
transduction pathway functions in the early drosophila embryo to
establish dorsal ventral polarity
--> interactions - pelle - toll receptor - tube
tube and pelle are required to relay the signal from toll to the
dorsal cactus complex
--> dorsal - cactus - complex
in a yeast two hybrid assay, we found that both tube and pelle
interact with dorsal
--> tube - pelle - interact - dorsal
tube interacts with dorsal via its c terminal domain, whereas full
length pelle is required for dorsal binding
--> tube - interacts - dorsal
--> pelle - required - dorsal binding
tube and pelle bind dorsal in the n terminal domain 1 of the dorsal
rel homology region rather than at the cactus binding site
--> tube - pelle - bind - dorsal
we propose a model in which tube, pelle, cactus, and dorsal form a
multimeric complex that represents an essential aspect of signal
transduction.
--> tube - pelle - cactus - dorsal - form - complex
activation of the kinase pelle by tube in the dorsoventral signal
transduction pathway of drosophila embryo
--> activation - pelle - by tube
in addition, pelle and tube interact directly with one another
--> pelle - tube - interact
we propose that tube is a direct activator of the protein kinase pelle.
--> tube - activator - pelle
interaction of the pelle kinase with the membrane associated protein
tube is required for transduction of the dorsoventral signal in
drosophila embryos
--> interaction - pelle - tube
we also find that tube sequences required for signaling interact
with pelle in a yeast two hybrid assay
--> tube - interact - pelle
we propose a model wherein tube activates pelle by recruiting it to
the plasma membrane, thereby propagating the axis determining signal.
--> tube - activates - pelle
tube and pelle then transduce the signal from activated toll to a
complex of dorsal and cactus
--> tube - pelle - transduce signal from - toll - to - complex - dorsal
- cactus
together, these results strongly support the hypothesis that
intracellular signaling requires the toll mediated formation of a
membrane associated complex containing both tube and pelle.
--> complex - tube - pelle
a cell surface signal relayed by toll, tube and pelle releases the
rel related protein dorsal from its cytoplasmic inhibitor cactus
--> cactus - inhibitor - dorsal
we show that dorsal binds specifically to tube, pelle and cactus,
and that the protein kinase activity of pelle differentially regulates
its interactions with dorsal and tube
--> dorsal - binds - tube - pelle - cactus
binding of extracellular ligand activates the transmembrane receptor
toll, which requires the novel protein tube to activate the
cytoplasmic serine threonine kinase pelle
--> tube - activate - pelle
2.) Conclusions
The actors
----------
dorsal: transcription factor
toll: a transmembrane receptor
pelle: a serine threonine protein kinase
tube: unknown function - associated to the membrane
spatzle: an extracellular ligand for toll
cactus: inhibitor of dorsal
(no sinonyms in virtual fly)
The events
----------
dorsal and cactus form an cytoplasmatic complex
spatzle arrives to the cell surface where it binds to a
receptor called toll
pelle arrives to the cell surface where it binds/phosphorylates to
tube which is associated to the membrane
activated toll induces a localized recruitment of tube and pelle to
the plasma membrane
pelle/tube bind dorsal (bound to cactus)
i.e. they form a complex of four components
pelle phosphorylates cactus
phosphorylation of cactus produces the release and degradation
of cactus and then dorsal translocates into the nucleus and
directs gene expression (establishing the dorsal ventral polarity
of early drosophila embryo)
b.) Full description of interactions in the Drosophila cell cycle control example
Cdk7 -> phosphorylation -> cak (1)
Cdk7 -> phosphorylation -> cdk2 (1)
Cdk7 -> suppress -> cak (1)
Cdk activating kinase -> phosphorylate -> cdc2 (1)
Cdk activating kinase -> phosphorylate -> cdk2 (1)
Cdk activating kinase -> phosphorylation -> cdk2 (1)
CycE -> phosphorylation -> cdk2 (2)
CycE -> phosphorylation -> cyclin A (1)
DEAD box RNA helicase -> suppress -> wee1 (1)
DP -> activate -> PCNA (1)
DP -> activate -> myc (1)
DP -> binding -> E2F (15)
DP -> inhibited -> cdk2 (1)
DP -> inhibited -> cyclin A (1)
DP -> interact -> E2F (10)
DP -> phosphorylation -> cdk2 (1)
DP -> phosphorylation -> cyclin A (1)
DP -> regulate -> E2F (2)
DP -> regulation -> E2F (4)
DP -> target -> E2F (1)
E2F -> activate -> DP (1)
E2F -> activate -> PCNA (1)
E2F -> activate -> myc (2)
E2F -> associated with -> cdk2 (1)
E2F -> associated with -> cyclin A (3)
E2F -> binding -> PCNA (3)
E2F -> binding -> cyclin A (10)
E2F -> binding -> cyclin D (1)
E2F -> binding -> cyclin E (2)
E2F -> binds -> DP (2)
E2F -> binds -> myc (4)
E2F -> inhibited -> cdk2 (1)
E2F -> inhibited -> cyclin A (1)
E2F -> inhibited -> cyclin D (1)
E2F -> interact -> cdk2 (1)
E2F -> interact -> cyclin A (5)
E2F -> interact -> cyclin E (1)
E2F -> phosphorylate -> cdk2 (7)
E2F -> phosphorylate -> cyclin A (7)
E2F -> phosphorylate -> cyclin E (1)
E2F -> phosphorylation -> cdk2 (6)
E2F -> phosphorylation -> cyclin A (8)
E2F -> regulate -> G1 Cyclin (1)
E2F -> regulate -> Myb (1)
E2F -> regulate -> cdc2 (1)
E2F -> regulate -> cdk2 (2)
E2F -> regulate -> cyclin A (4)
E2F -> regulate -> cyclin D (1)
E2F -> regulate -> cyclin E (1)
E2F -> regulation -> PCNA (1)
E2F -> regulation -> Proliferating cell nuclear antigen (1)
E2F -> suppress -> DP (1)
E2F -> target -> cyclin E (2)
E2F -> target -> p21 (1)
G1 Cyclin -> binds -> cdk2 (1)
G1 Cyclin -> binds -> cyclin B (1)
G1 Cyclin -> phosphorylation -> cdc2 (1)
Myb -> binding -> E2F (4)
PCNA -> binding -> cyclin D (2)
PCNA -> binding -> cyclin dependent kinase inhibitor (2)
PCNA -> binds -> p21 (1)
PCNA -> inhibited -> p21 (1)
PCNA -> target -> E2F (1)
Proliferating cell nuclear antigen -> binding -> PCNA (1)
Proliferating cell nuclear antigen -> binding -> cyclin D (1)
Proliferating cell nuclear antigen -> binding -> cyclin dependent kinase inhibitor (1)
RBF -> phosphorylate -> cyclin E (1)
RBF -> regulate -> E2F (1)
RBF -> regulate -> cyclin E (1)
cak -> activate -> cdc2 (1)
cak -> activate -> cdk2 (1)
cak -> inhibited -> Cdk7 (1)
cak -> phosphorylate -> Cdk7 (1)
cak -> phosphorylate -> cdk2 (2)
cdc2 -> activate -> cyclin B (2)
cdc2 -> activate -> cyclin D (1)
cdc2 -> activate -> twine (1)
cdc2 -> binding -> Myb (1)
cdc2 -> binding -> wee1 (1)
cdc2 -> inhibited -> wee1 (1)
cdc2 -> interact -> E2F (2)
cdc2 -> interact -> wee1 (1)
cdc2 -> phosphorylate -> cyclin B (3)
cdc2 -> regulate -> mpf (1)
cdk2 -> activate -> Cdk7 (1)
cdk2 -> activate -> cdc2 (1)
cdk2 -> activate -> cyclin A (1)
cdk2 -> activate -> cyclin h (1)
cdk2 -> associated with -> Cdk7 (1)
cdk2 -> associated with -> cdc2 (1)
cdk2 -> associated with -> cyclin A (4)
cdk2 -> associated with -> cyclin D (1)
cdk2 -> associated with -> cyclin E (1)
cdk2 -> associated with -> cyclin h (1)
cdk2 -> associated with -> p21 (2)
cdk2 -> binding -> DP (1)
cdk2 -> binding -> E2F (2)
cdk2 -> binding -> Proliferating cell nuclear antigen (1)
cdk2 -> binding -> cyclin A (1)
cdk2 -> binding -> cyclin D (1)
cdk2 -> binding -> p21 (1)
cdk2 -> binds -> DP (1)
cdk2 -> binds -> E2F (1)
cdk2 -> inhibited -> cyclin D (4)
cdk2 -> inhibited -> cyclin E (1)
cdk2 -> inhibited -> p21 (3)
cdk2 -> interact -> cyclin A (1)
cdk2 -> phosphorylate -> Cdk1 (2)
cdk2 -> phosphorylate -> Cdk7 (4)
cdk2 -> phosphorylate -> cdc2 (2)
cdk2 -> phosphorylate -> cdks (1)
cdk2 -> phosphorylate -> cyclin h (4)
cdk2 -> phosphorylation -> cyclin E (6)
cdk2 -> phosphorylation -> myc (1)
cdk2 -> target -> cyclin D (1)
cdks -> activate -> E2F (1)
cdks -> phosphorylation -> Cdk activating kinase (1)
cdks -> phosphorylation -> cdk2 (1)
cdks -> phosphorylation -> cyclin A (1)
cdks -> regulate -> E2F (1)
cyclin A -> activate -> Cdk1 (1)
cyclin A -> activate -> E2F (2)
cyclin A -> activate -> Myb (1)
cyclin A -> activate -> cyclin B (2)
cyclin A -> activate -> cyclin D (4)
cyclin A -> activate -> myc (1)
cyclin A -> activate -> p34cdc2 (1)
cyclin A -> associated with -> p21 (1)
cyclin A -> associated with -> p34cdc2 (1)
cyclin A -> binding -> DP (2)
cyclin A -> binding -> cdc2 (2)
cyclin A -> binding -> cyclin D (2)
cyclin A -> binding -> myc (1)
cyclin A -> binds -> DP (1)
cyclin A -> binds -> E2F (1)
cyclin A -> binds -> cdc2 (1)
cyclin A -> binds -> cdk2 (1)
cyclin A -> inhibited -> cdk2 (2)
cyclin A -> inhibited -> cyclin D (2)
cyclin A -> inhibited -> p21 (1)
cyclin A -> phosphorylate -> Cdk1 (2)
cyclin A -> phosphorylate -> cdk2 (6)
cyclin A -> phosphorylate -> cdks (1)
cyclin A -> phosphorylate -> cyclin D (1)
cyclin A -> phosphorylate -> cyclin E (4)
cyclin A -> phosphorylation -> cdc2 (2)
cyclin A -> phosphorylation -> cdk2 (3)
cyclin A -> regulation -> DP (1)
cyclin A -> regulation -> E2F (4)
cyclin A -> regulation -> cyclin D (1)
cyclin A -> target -> cyclin D (1)
cyclin B -> activate -> cyclin D (2)
cyclin B -> associated with -> cdc2 (2)
cyclin B -> associated with -> p34cdc2 (1)
cyclin B -> binding -> cdc2 (4)
cyclin B -> binds -> cdks (2)
cyclin B -> binds -> p21 (2)
cyclin B -> binds -> p34cdc2 (1)
cyclin B -> inhibited -> cdc2 (1)
cyclin B -> inhibited -> cyclin A (1)
cyclin B -> inhibited -> p34cdc2 (1)
cyclin B -> interact -> cdc2 (2)
cyclin B -> interact -> cdk2 (1)
cyclin B -> phosphorylate -> p34cdc2 (4)
cyclin B -> phosphorylation -> Cdk activating kinase (1)
cyclin B -> phosphorylation -> cdc2 (8)
cyclin B -> phosphorylation -> cyclin A (2)
cyclin B -> phosphorylation -> p34cdc2 (5)
cyclin B -> regulation -> cdc2 (2)
cyclin B2 -> phosphorylation -> p34cdc2 (1)
cyclin D -> activate -> Cdk7 (1)
cyclin D -> activate -> E2F (3)
cyclin D -> activate -> cdk2 (5)
cyclin D -> activate -> cyclin E (2)
cyclin D -> activate -> cyclin h (1)
cyclin D -> activate -> p21 (1)
cyclin D -> associated with -> Cdk7 (1)
cyclin D -> associated with -> E2F (2)
cyclin D -> associated with -> cyclin h (1)
cyclin D -> binding -> myc (1)
cyclin D -> binds -> cdks (2)
cyclin D -> binds -> p21 (2)
cyclin D -> inhibited -> bHLH (1)
cyclin D -> inhibited -> cyclin E (1)
cyclin D -> inhibited -> p21 (1)
cyclin D -> interact -> PCNA (2)
cyclin D -> phosphorylate -> Cdk7 (3)
cyclin D -> phosphorylate -> E2F (1)
cyclin D -> phosphorylate -> cdk2 (5)
cyclin D -> phosphorylate -> cyclin B (1)
cyclin D -> phosphorylate -> cyclin h (3)
cyclin D -> phosphorylation -> Cdk activating kinase (1)
cyclin D -> phosphorylation -> E2F (5)
cyclin D -> regulate -> cdk2 (1)
cyclin D -> regulation -> E2F (1)
cyclin E -> activate -> E2F (3)
cyclin E -> activate -> Myb (1)
cyclin E -> activate -> cdc2 (2)
cyclin E -> activate -> cdk2 (4)
cyclin E -> associated with -> E2F (2)
cyclin E -> binding -> Proliferating cell nuclear antigen (1)
cyclin E -> binding -> cdk2 (2)
cyclin E -> binding -> cyclin A (1)
cyclin E -> binding -> p21 (2)
cyclin E -> binds -> cdk2 (2)
cyclin E -> inhibited -> p21 (2)
cyclin E -> interact -> cdk2 (3)
cyclin E -> interact -> cyclin A (1)
cyclin E -> modulate -> cdk2 (1)
cyclin E -> phosphorylate -> Cdk1 (2)
cyclin E -> phosphorylate -> cdk2 (5)
cyclin E -> phosphorylate -> cdks (1)
cyclin E -> phosphorylate -> cyclin D (2)
cyclin E -> phosphorylation -> CycE (1)
cyclin E -> phosphorylation -> E2F (2)
cyclin E -> phosphorylation -> cdc2 (1)
cyclin E -> phosphorylation -> cyclin A (2)
cyclin E -> regulate -> cdc2 (1)
cyclin E -> regulate -> cdk2 (2)
cyclin E -> regulate -> roughex (1)
cyclin E -> regulation -> cyclin A (1)
cyclin E -> regulation -> string (1)
cyclin dependent kinase inhibitor -> interact -> PCNA (2)
cyclin h -> phosphorylation -> cak (1)
cyclin h -> phosphorylation -> cdk2 (1)
dmcyce -> regulate -> cyclin E (1)
dpp -> interact -> cyclin E (1)
gadd45 -> binds -> PCNA (1)
mpf -> phosphorylation -> p34cdc2 (2)
myc -> activate -> cdk2 (1)
myc -> activate -> cyclin E (1)
myc -> activate -> p21 (1)
myc -> binding -> E2F (7)
myc -> regulate -> E2F (1)
myc -> regulation -> E2F (3)
myc -> stimulate -> E2F (1)
myc -> target -> E2F (2)
p21 -> associated with -> cyclin E (1)
p21 -> binding -> PCNA (5)
p21 -> binding -> Proliferating cell nuclear antigen (1)
p21 -> binding -> rfc (1)
p21 -> inhibited -> E2F (1)
p21 -> interact -> PCNA (4)
p21 -> regulate -> PCNA (1)
p21 -> regulate -> cdc2 (1)
p21 -> regulate -> cyclin B (1)
p21 -> regulate -> cyclin D (1)
p21 -> regulation -> cdk2 (1)
p21 -> regulation -> cyclin E (1)
p21 -> suppress -> E2F (1)
p21 -> target -> cyclin D (1)
p34cdc2 -> inhibited -> cyclin A (1)
p34cdc2 -> phosphorylation -> Protein phosphatase 2A (1)
p34cdc2 -> phosphorylation -> cyclin A (1)
p34cdc2 -> regulate -> E2F (2)
p34cdc2 -> regulate -> Protein phosphatase 2A (2)
p34cdc2 -> regulate -> cyclin D (1)
p34cdc2 -> regulate -> mpf (1)
rfc -> binding -> PCNA (2)
roughex -> binds -> cyclin E (2)
roughex -> destabilized -> cyclin E (1)
string -> binding -> c Myb (1)
string -> phosphorylation -> cdc2 (1)
twist -> activate -> bHLH (2)
twist -> binding -> bHLH (1)
twist -> interact -> bHLH (2)
ubiquitin -> regulate -> cdk2 (1)
wee1 -> activate -> cdc2 (1)
wee1 -> phosphorylate -> cdc2 (5)
wee1 -> phosphorylate -> cyclin D (1)
wee1 -> phosphorylate -> p34cdc2 (2)
wee1 -> phosphorylation -> cdc2 (4)
wee1 -> phosphorylation -> p34cdc2 (2)
wee1 -> regulate -> cdc2 (2)
wee1 -> regulate -> p34cdc2 (2)
wee1 -> regulation -> cdc2 (2)
wee1 -> suppress -> p34cdc2 (1)
wee1 kinase -> activate -> cdc2 (2)
wee1 kinase -> phosphorylate -> cdc2 (1)
wee1 kinase -> phosphorylate -> cyclin B (1)
wee1 kinase -> phosphorylate -> p34cdc2 (1)
wee1 kinase -> phosphorylation -> cdc2 (4)
wee1 kinase -> phosphorylation -> cyclin B (3)
wee1 kinase -> regulate -> cdc2 (1)
wee1 kinase -> regulate -> cyclin B (1)
c.) Sentences used for the analysis of the Drosophila cell cycle control network
MED 0:
actions: interact; interaction;
Proteins: DP; E2F;
physiological e2f arises when members of two distinct families of proteins
interact as e2f dp heterodimers, in which the e2f component mediates
transcriptional activation and the physical interaction with pocket
proteins, such as the tumour suppressor protein prb
MED 89174977:
actions: interact;
Proteins: cyclin B; cdc2;
since the first meiotic division in clams can proceed even when new protein
synthesis is blocked, these results strongly suggest it is the
fertilization triggered unmasking of cyclin b protein that drives cells
into meiosis i. we propose that the unmasking of maternal cyclin b protein
allows it to interact with cdc2 protein kinase, which is also stored in
oocytes, and that the formation of this cyclin b cdc2 complex generates
active m phase promoting factor.
MED 89252827:
actions: regulated; target;
Proteins: myc; E2F;
the human myc promoter is the first cellular target described for e2f. the
results suggest that expression of myc might be regulated via modulation of
e2f by cellular 'e1a like' factors.
MED 89264470:
actions: activated;
Proteins: myc; E2F;
the myc promoter can be trans activated in an e1a dependent manner and site
directed mutagenesis demonstrates that these e2f elements are essential
for trans activation
MED 89264470:
actions: binds; binds to;
Proteins: myc; E2F;
here we show that e2f binds to two sequence elements within the p2 promoter
of the human myc gene which are within a region that is critical for
promoter activity
MED 90108666:
actions: binds; binds to;
Proteins: myc; E2F;
nuclear factor e2f is a cellular protein that binds to the adenovirus e2
promoter and e1a enhancer regions and to the cellular c myc p2 promoter
region
MED 90360999:
actions: associated with;
Proteins: cyclin A; p34cdc2;
the cyclin a polypeptide is associated with a protein that cross reacts
with an antibody against the conserved 'pstair' epitope of p34cdc2, and the
cyclin a cdc2 complex exhibits protein kinase activity that oscillates with
the cell cycle
MED 91060064:
actions: interaction;
Proteins: wee1; cdc2;
also, like wee1 and cdc2 w, stf1 suppression of cdc25 is reversed by
overexpression of the putative type 1 protein phosphatase bws1+ dis2+.
interaction with various mutants and plasmid overexpression experiments
suggest that stf1 does not operate either upstream or downstream of wee1
MED 91160055:
actions: regulate;
Proteins: mpf; cdc2;
these biochemical experiments demonstrate that the cdc25 protein actively
drives tyrosine dephosphorylation of the cdc2 protein and offer the
prospect for characterizing the individual factors that regulate the
activation of mpf during the progression from s phase to mitosis.
MED 91168259:
actions: phosphorylation;
Proteins: wee1; cdc2;
wee1 acts antagonistically to cdc25 in the tyrosine dephosphorylation and
activation of cdc2, yet biochemical evidence suggests that wee1 is not
required for tyrosine phosphorylation and its role is obscure
MED 91168259:
actions: regulation;
Proteins: wee1; cdc2;
we show here that a related 66 kd kinase, called mik1, acts redundantly
with wee1 in the negative regulation of cdc2 in s. pombe
MED 91224105:
actions: binds;
Proteins: p34cdc2; cyclin B;
these results show that, as it is synthesized, cyclin b binds and recruits
p34cdc2 for tyrosine phosphorylation
MED 91224105:
actions: phosphorylated;
Proteins: p34cdc2; cyclin B;
in late g2, it is present as an inactive complex of tyrosine
phosphorylated p34cdc2 and unphosphorylated cyclin bcdc13
MED 91224105:
actions: phosphorylation;
Proteins: p34cdc2; mpf;
in m phase, its activation as an active mpf displaying histone h1 kinase
originates from the concomitant tyrosine dephosphorylation of the p34cdc2
subunit and the phosphorylation of the cylin bcdc13 subunit
MED 91251904:
actions: phosphorylation;
Proteins: p34cdc2; cyclin B;
oocytes arrested in the g2 phase of the cell cycle contain a p34cdc2 cyclin
b complex which is kept in an inactive form by phosphorylation of its
p34cdc2 subunit on tyrosine, threonine and perhaps serine residues
MED 91292527:
actions: binding; interaction; regulation;
Proteins: cyclin A; E2F;
cell cycle regulation of the e2f transcription factor involves an
interaction with cyclin a. we have examined e2f binding activity in
extracts of synchronized nih 3t3 cells
MED 91370055:
actions: phosphorylation;
Proteins: Protein phosphatase 2A; p34cdc2;
p34cdc2 phosphorylation sites in histone h1 are dephosphorylated by protein
phosphatase 2a1
MED 92005673:
actions: activated;
Proteins: cdc2; cyclin E;
cyclin e produced in e. coli bound and activated the cdc2 protein in
extracts from human g1 cells, and antibodies against cyclin e
immunoprecipitated a histone h1 kinase from hela cells
MED 92005691:
actions: regulates;
Proteins: p34cdc2; mpf;
therefore, cdc25 is a specific protein phosphatase that dephosphorylates
tyrosine and possibly threonine residues on p34cdc2 and regulates mpf
activation.
MED 92011851:
actions: associated with;
Proteins: p34cdc2; cyclin B;
cyclin b1 is associated with p34cdc2 in the cytoplasm
MED 92042220:
actions: binding;
Proteins: PCNA; Proliferating cell nuclear antigen;
lag times in dna synthesis by dna polymerase delta holoenzyme were due to
atp mediated formation of an initiation complex on the primed dna by the
polymerase with the proliferating cell nuclear antigen and replication
factor c. lag time analysis showed that high affinity binding of rf c to
the primer terminus required pcna and that this complex was recognized by
the polymerase
MED 92057166:
actions: regulated;
Proteins: Protein phosphatase 2A; p34cdc2;
the mechanism of activation of p34cdc2 is negatively regulated by a form of
protein phosphatase 2a. ovulated vertebrate oocytes are arrested at
metaphase of the second meiotic division under the control of the proto
oncogene c mos a protein kinase
MED 92097551:
actions: activate;
Proteins: cyclin B; cdc2; cyclin D;
this functional difference between the two cyclin types, the first to be
described, provides strong support for the idea that the two cyclins have
different roles in the cell cycle and suggests that one specialized role of
the cyclin b cdc2 complex is to activate the cyclin destruction pathway and
drive cells into interphase of the next cell cycle.
MED 92097551:
actions: activates;
Proteins: cyclin B; cyclin D;
when added to emetine arrested interphase lysates devoid of endogenous
cyclins, only cyclin b delta 97 activates the cyclin destruction system
MED 92119711:
actions: interacts; regulated;
Proteins: cyclin A; E2F;
the transcription factor e2f interacts with the retinoblastoma product and
a p107 cyclin a complex in a cell cycle regulated manner
MED 92127590:
actions: regulation;
Proteins: cyclin B; cdc2;
these results suggest that the mechanism by which cdc25 triggers cdc2
activation involves a periodic physical association between cdc25 and the
cyclin b cdc2 complex and also that mitotic control can be affected by
mechanisms other than transcriptional regulation of the cdc25 gene.
MED 92192031:
actions: associated with;
Proteins: cyclin A; E2F;
in addition, cyclin a is associated with the e2f transcription factor in a
complex which is dissociated by the e1a oncogene product
MED 92192031:
actions: binds;
Proteins: cyclin A; cdk2; cdc2;
cyclin a binds both cdk2 and cdc2, giving two distinct cyclin a kinase
activities, one appearing in s phase, the other in g2
MED 92212922:
actions: activated; regulation;
Proteins: cyclin A; cyclin D;
human cyclin dependent kinase 2 is activated during the s and g2 phases of
the cell cycle and associates with cyclin a. we have analyzed the cell
cycle regulation of human cyclin dependent kinase 2, a protein closely
related to the cell cycle regulatory protein kinase cdc2
MED 92212922:
actions: associated with; regulate;
Proteins: cyclin A; cdk2; cdc2;
active s phase cdk2 migrates in multiple large complexes on gel filtration,
and cdk2 in one of these complexes is associated with cyclin a. these
findings suggest that cdk2 and cdc2, in association with distinct cyclins,
regulate separate functions in the mammalian cell cycle.
MED 92321694:
actions: phosphorylated;
Proteins: p34cdc2; cyclin B;
in late g2, it is present as an inactive complex of tyrosine
phosphorylated p34cdc2 and unphosphorylated cyclin bcdc13
MED 92381098:
actions: activated; phosphorylation;
Proteins: cyclin B; cdc2;
okadaic acid activated cyclin b cdc2 kinase and strongly reduced tyrosine
phosphorylation of cyclin b associated cdc2, even in the presence of
vanadate
MED 92381098:
actions: phosphorylation;
Proteins: cyclin A; cyclin B; cdc2;
cyclin b associated cdc2 does not undergo detectable phosphorylation on
tyrosine in egg extracts containing active cyclin a cdc2 kinase, even in
the presence of vanadate
MED 93012944:
actions: associated with; regulated;
Proteins: E2F; cyclin E;
we report here that cyclin e is found associated with the transcription
factor e2f in a temporally regulated fashion
MED 93012944:
actions: associated with; regulated;
Proteins: cyclin A; cdk2; E2F; cyclin E;
therefore, the p107 e2f complex is associated with two different cdk2
kinase complexes one containing cyclin a and the other containing cyclin e
and the appearance of these complexes is temporally regulated during the
cell cycle
MED 93030713:
actions: phosphorylated;
Proteins: p34cdc2; cyclin B; wee1 kinase;
the human wee1 kinase phosphorylated the p34cdc2 cyclin b complex on
tyrosine 15 but not on threonine 14 in vitro and inactivated the p34cdc2
cyclin b kinase
MED 93030713:
actions: phosphorylates; regulates;
Proteins: p34cdc2; cyclin B;
these results indicate that the product of the wee1hu gene directly
regulates the p34cdc2 cyclin b complex in human cells and that a kinase
other than that encoded by wee1hu phosphorylates p34cdc2 on threonine 14.
MED 93030713:
actions: regulates;
Proteins: wee1; p34cdc2; cyclin B;
the wee1+ kinase negatively regulates mitosis by phosphorylating p34cdc2 on
tyrosine 15, thereby inactivating the p34cdc2 cyclin b complex
MED 93030749:
actions: regulated;
Proteins: cyclin A; cdk2; E2F;
the disruption of this e2f rb interaction, as well as a complex involving
e2f in association with the cell cycle regulated cyclin a cdk2 kinase
complex, may be a common mechanism of action for the oncoproteins encoded
by the dna tumor viruses.
MED 93078736:
actions: associated with; binding;
Proteins: cyclin A; E2F;
we tested the deleted proteins for the ability to bind to viral oncoprotein
e1a and to the transcription factor e2f. we also measured the ability of
the mutant proteins to become hyperphosphorylated in vivo and to be
recognized as substrates in vitro by a cell cycle regulatory kinase
associated with cyclin a. we identified two regions of prb that are
required for e2f binding and for hyperphosphorylation
MED 93130682:
actions: activated;
Proteins: cyclin A; p34cdc2; cyclin B;
a cyclin a p33 complex is activated at g1 s. we have assembled active
cyclin b1 p34cdc2 complex in insect cells
MED 93130684:
actions: activated;
Proteins: cyclin A; cdk2;
the two complexes appear in s phase but cyclin a cdk2 is activated earlier
than cyclin a cdc2
MED 93130684:
actions: binding; phosphorylation; stimulates;
Proteins: cyclin A; cdc2;
we have identified a novel 'activating factor' that stimulates binding
between cyclin and cdc2 by inducing phosphorylation of cdc2 on thr161
MED 93130687:
actions: phosphorylation; regulation;
Proteins: p34cdc2; cyclin B;
regulation of p34cdc2 protein kinase activity by phosphorylation and cyclin
binding
MED 93140757:
actions: activate; binding; regulation;
Proteins: cyclin A; cyclin B; cdc2; cyclin D;
sequences within the conserved cyclin box of human cyclin a are sufficient
for binding to and activation of cdc2 kinase. cyclins are pivotal in the
coordinate regulation of the cell cycle. by physical association, they are
able to activate at least one of the cyclin dependent kinases, cdc2
MED 93154346:
actions: activate;
Proteins: cyclin B; cdc2;
cdc25 c is able to activate cdc2 cyclin b1 in xenopus egg extracts and to
induce xenopus oocyte maturation, but only after stable thiophosphorylation
MED 93154348:
actions: phosphorylates;
Proteins: wee1; p34cdc2;
contrary to the dual specificity kinase hypothesis, purified human wee1
phosphorylates p34cdc2 exclusively on tyr15 in vitro
MED 93180815:
actions: phosphorylated;
Proteins: p34cdc2; cyclin B;
the apparent km for modification of wild type, monomeric p34cdc2 was 148
microm fsba and was not significantly affected by association with cyclin
b. tyrosine phosphorylated p34cdc2 was modified by fsba with a slightly
higher km
MED 93180815:
actions: phosphorylation; regulated;
Proteins: p34cdc2; cyclin D;
in addition to being negatively regulated by phosphorylation, the kinase
activity of p34cdc2 was positively regulated by the cyclin dependent
phosphorylation of thr 161
MED 93188967:
actions: binding;
Proteins: DP; E2F;
mutant rb proteins isolated from tumour cells are unable to bind drtf1 e2f,
and certain viral oncoproteins, such as adenovirus e1a, sequester rb and
p107 in order to free active drtf1 e2f. here we report the isolation of a
complementary dna encoding drtf1 polypeptide 1, a major sequence specific
binding protein that is present in drtf1 e2f, including rb and p107
associated drtf1 e2f. the dna binding domain of dp 1 contains a region that
resembles that of e2f 1, and recognizes the same sequence
MED 93204974:
actions: interacts;
Proteins: cyclin B; cdc2;
two fission yeast b type cyclins, cig2 and cdc13, have different functions
in mitosis cyclin b interacts with cdc2 kinase to induce cell cycle events,
particularly those of mitosis
MED 93208887:
actions: phosphorylation; suppresses;
Proteins: wee1; p34cdc2;
the wee1 protein kinase suppresses the entry into mitosis by mediating the
inhibitory tyrosine phosphorylation of p34cdc2
MED 93216860:
actions: activate; binding;
Proteins: cyclin A; cdc2;
we now show, using biologically active fusion proteins, that cyclin a can
direct the binding of the cdc2 like kinase subunit, p33cdk2, to complexed
drtf1, containing either rb or p107, as well as activate its histone h1
kinase activity
MED 93238944:
actions: binding;
Proteins: myc; E2F;
gal1 based promoter constructs carrying the e2f binding site of the myc or
the adenovirus e2 promoter showed transcriptional activity in yeast cells
MED 93238944:
actions: binding;
Proteins: myc; E2F;
ye2f showed identical contact points within the myc binding site as
authentic e2f protein from mammalian cells
MED 93238944:
actions: regulation; target;
Proteins: myc; E2F;
the promoter of the human proto oncogene myc has been the first cellular
target shown to be subject to regulation by the e2f transcription factor
MED 93283735:
actions: inhibited; phosphorylated; phosphorylation;
Proteins: cyclin A; p34cdc2; cyclin B;
we propose that this specific inhibition of cdc25 c dephosphorylation is
part of a positive feedback loop that also involves direct phosphorylation
and activation of cdc25 c by p34cdc2 cyclin b. dephosphorylation of cdc25 c
is also inhibited when cyclin a dependent protein kinase is active, and
this may explain the potentiation of p34cdc2 cyclin b protein kinase
activation by cyclin a. in extracts supplemented with nuclei, the block on
p34cdc2 cyclin b activation by unreplicated dna is abolished when pp 2a is
inhibited or when stably phosphorylated cdc25 c is added, but not when pp 1
is specifically inhibited
MED 93295488:
actions: binding; inhibited; phosphorylation;
Proteins: cyclin B; cdc2;
in most species, including the fission yeast schizosaccharomyces pombe, the
cdc2 cyclin b mitosis inducing kinase is maintained in an inhibited state
during interphase as a result of phosphorylation of a tyrosine residue in
the atp binding region of cdc2
MED 93327760:
actions: binding;
Proteins: Myb; E2F;
specific g0 and s phase e2f complexes binding to this b myb element were
detected in nih3t3 cell extracts by mobility shift assays
MED 93327760:
actions: binding; regulated;
Proteins: Myb; E2F;
an e2f binding site mediates cell cycle regulated repression of mouse b
myb transcription
MED 93351227:
actions: activated;
Proteins: wee1; cdc2;
human wee1 maintains mitotic timing by protecting the nucleus from
cytoplasmically activated cdc2 kinase
MED 93351227:
actions: activated;
Proteins: wee1 kinase; cdc2;
the human wee1 kinase appears to coordinate the transition between dna
replication and mitosis by protecting the nucleus from this cytoplasmically
activated cdc2 kinase.
MED 93360962:
actions: phosphorylation;
Proteins: cyclin A; E2F;
thus, changes in cyclin a expression and prb phosphorylation are not
primary events that influence the pattern of e2f responses to cytokines
MED 94010284:
actions: inhibited; interaction;
Proteins: DP; E2F;
finally, we demonstrate that e2f 1 and dp 1 association is required for
stable interaction with prb in vivo and that trans activation by e2f 1 dp 1
heterodimers is inhibited by prb
MED 94038914:
actions: binding;
Proteins: DP; E2F;
we report here that dp 1 and e2f 1 exist in a dna binding complex in vivo
and that they bind efficiently and preferentially as a heterodimer to the
e2f site
MED 94038914:
actions: interact;
Proteins: DP; E2F;
moreover, studies in yeast and drosophila cells indicate that dp 1 and e2f
1 interact synergistically in e2f site dependent transcriptional activation.
MED 94061996:
actions: binding; phosphorylation;
Proteins: cyclin A; cdk2; cyclin D; cdks; cyclin E;
p21cip1 is a potent, tight binding inhibitor of cdks and can inhibit the
phosphorylation of rb by cyclin a cdk2, cyclin e cdk2, cyclin d1 cdk4, and
cyclin d2 cdk4 complexes
MED 94074542:
actions: phosphorylation; regulates;
Proteins: wee1; cdc2;
the wee1 protein kinase negatively regulates the entry into mitosis by
catalyzing the inhibitory tyrosine phosphorylation of the cdc2 protein
MED 94116862:
actions: activate;
Proteins: cdk2; cyclin E;
these growth inhibitory signals block cdk2 activation by raising the
threshold level of cyclin e necessary to activate cdk2
MED 94116862:
actions: binds; binds to;
Proteins: cdk2; cyclin E;
in arrested cells the threshold is set higher than physiological cyclin e
levels and is determined by an inhibitor that binds to cyclin e cdk2
complexes
MED 94116862:
actions: regulate;
Proteins: cdk2; cyclin D;
cyclin d2 cdk4 complexes bind competitively to and down regulate the
activity of p27 and may thereby act in a pathway that reverses cdk2
inhibition and enables g1 progression.
MED 94151028:
actions: activates; regulated;
Proteins: cdk2; cdc2; cyclin E;
inducible acceleration of g1 progression through tetracycline regulated
expression of human cyclin e. cyclin e is a cell cycle regulated protein
that activates the cdc2 related protein kinases cdk2 shortly before s
phase entry
MED 94155851:
actions: binding; regulated;
Proteins: Myb; E2F;
regulation of the b myb promoter in nih3t3 cells correlates with binding of
distinct p107 containing complexes at the e2f binding site, and analysis of
e7 mutants confirms that b myb transcription in these cells is regulated
through interactions with p107 rather than prb
MED 94170989:
actions: phosphorylation;
Proteins: cdc2; string;
during interphase 14, programmed degradation of maternal string protein
leads to inhibitory phosphorylation of cdc2 and cell cycle arrest
MED 94266993:
actions: interaction;
Proteins: cyclin B; cdk2; cyclin E;
our findings also indicate that the cyclin box in cyclin e mediates the
interaction with cdk2.
MED 94268843:
actions: activates; binding;
Proteins: myc; cyclin A; E2F; cyclin D;
furthermore, overexpression of cyclin a strongly activates the myc promoter
and this effect is further enhanced by coexpression of e2f 1 and cyclin a.
we also find that expression of g1 phase cyclin d1 leads to an e2f binding
site dependent trans activation of the myc promoter and that this
activation can be abrogated by overexpression of rb
MED 94268843:
actions: binding;
Proteins: myc; E2F;
regulation of myc promoter activity critically depends on the presence of a
binding site for transcription factor e2f. human e2f has been implicated
also in the control of cell cycle progression through it association with
the retinoblastoma suppressor gene product rb, and with multimeric protein
complexes containing the g1 s and s phase cyclins e and a, respectively
MED 94274689:
actions: regulate; regulated; regulation;
Proteins: myc; p34cdc2; E2F;
the genes encoding thymidine kinase and p34cdc2 are regulated with kinetics
similar to those observed for changes in the macromolecular state of e2f.
however, regulation of c myc expression occurs long before any change in
e2f. the macromolecular state of e2f may regulate expression of genes at
the g1 s boundary
MED 94274689:
actions: regulation;
Proteins: myc; E2F;
however, the data are not consistent with the hypothesis that association
of e2f with tumor suppressor gene products such as p107 or p105rb 1 is
relevant to glucocorticoid regulation of c myc transcription.
MED 94274689:
actions: regulation;
Proteins: myc; E2F;
the macromolecular state of the transcription factor e2f and glucocorticoid
regulation of c myc transcription
MED 94309646:
actions: inhibited; phosphorylation;
Proteins: cyclin D; bHLH;
ectopic expression of cyclin d1 inhibited the activity of a myogenic bhlh
regulator mutant lacking the basic region protein kinase c site, indicating
that phosphorylation of this site is not relevant to the mechanism of
inhibition
MED 94313991:
actions: binding; interact;
Proteins: DP; E2F;
two sequence specific dna binding proteins, dp 1 and e2f 1, are components
of drtf1 e2f which synergistically interact in a dp 1 e2f 1 heterodimer
MED 94313991:
actions: regulated;
Proteins: DP; E2F;
we conclude that dp 1 is a frequent and cell cycle regulated component of
drtf1 e2f, and that in the dp 1 e2f 1 heterodimer it is functionally
important for recognition by prb and the e4 orf 6 7 protein.
MED 94349374:
actions: activates; phosphorylates;
Proteins: cdk2; cdc2; cak;
the cak holoenzyme activates complexes of cdk2 and cdc2 with various
cyclins and also phosphorylates cdk2, but not cdc2, in the absence of cyclin
MED 94359612:
actions: binding; phosphorylation;
Proteins: cyclin B; Cdk activating kinase;
cdk activation is dependent on cyclin binding and phosphorylation of a
conserved threonine mediated by the cdk activating kinase cak
MED 95000711:
actions: binding; interacts;
Proteins: DP; E2F;
efficient dna binding activity arises when a dp protein interacts with an
e2f protein
MED 95018591:
actions: binding;
Proteins: DP; E2F;
e2f dna binding activity is composed of a heterodimer of related but
distinct proteins of the e2f 1 and dp 1 families
MED 95018591:
actions: interaction;
Proteins: DP; E2F;
dp 1 also is necessary for stable interaction with e4 6 7 and an internal
segment of dp 1 is required that is positioned in a location similar to
that of the conserved e2f 1 domain
MED 95021255:
actions: phosphorylates;
Proteins: cdk2; cdc2; Cdk activating kinase;
this step is catalyzed by a cdk activating kinase functionally analogous to
the enzyme which phosphorylates cdc2 and cdk2 at thr 161 160
MED 95047332:
actions: phosphorylate; phosphorylation;
Proteins: cyclin A; cdk2; E2F;
however, these cyclin kinase complexes exhibit differences in the ability
to phosphorylate e2f. only cyclin a cdk2 can phosphorylate e2f effectively,
and this phosphorylation abolishes its ability to bind dna and mediate
trans activation
MED 95047404:
actions: binding;
Proteins: DP; E2F;
like the other e2fs, e2f 4 requires dp 1 for efficient dna binding and
transcriptional activation of e2f site containing promoters
MED 95059071:
actions: binding;
Proteins: cyclin A; cdk2; E2F;
binding studies conducted both in vitro and in vivo demonstrated that the
cyclin a cdk2 binding region resided within the n terminal 124 amino acids
of e2f 1
MED 95059071:
actions: binding; binds;
Proteins: cyclin A; DP; cdk2; E2F;
cyclin a cdk2 binds directly to e2f 1 and inhibits the dna binding activity
of e2f 1 dp 1 by phosphorylation
MED 95059071:
actions: binding; inhibited; phosphorylation;
Proteins: cyclin A; DP; cdk2; E2F;
finally, we report that the dna binding activity of the e2f 1 dp 1 complex
is inhibited following phosphorylation by cyclin a cdk2.
MED 95059071:
actions: interaction; phosphorylation;
Proteins: cyclin A; cdk2; E2F;
we have analyzed e2f 1 phosphorylation and its interaction with cyclin a
cdk2 complexes both in vivo and in vitro
MED 95059071:
actions: phosphorylated;
Proteins: cyclin A; cdk2; E2F;
however, e2f 1 was phosphorylated by cyclin a cdk2 in vitro and was
phosphorylated in vivo in hela cells
MED 95060804:
actions: activate;
Proteins: E2F; cyclin D;
cyclin d1 can also activate the adenovirus e2 promoter via e2f. both
promoters are repressed by p16ink4 and this repression can be released by
overexpression of cdk4
MED 95060804:
actions: activate;
Proteins: E2F; cyclin D;
in addition, we show that both e2f sites bind complexes containing the
retinoblastoma protein and that in rb deficient cell lines overexpression
of cyclin d1 fails to activate e2f dependent transcription, indicating that
prb may be involved in promoter activation.
MED 95060804:
actions: regulation;
Proteins: E2F; cyclin D;
the data reported here support a direct role for cyclin d1 and its
associated kinase in cell cycle regulation of e2f activity and s phase
specific gene expression
MED 95074062:
actions: phosphorylates; phosphorylation; regulate;
Proteins: wee1; p34cdc2; cyclin B;
mik1+ and wee1+ function to regulate the tyrosine phosphorylation of
p34cdc2 in schizosaccharomyces pombe cell 64, 1111 1122 . wee1+ encodes a
tyrosine kinase that directly phosphorylates p34cdc2 on tyrosine 15,
resulting in the inactivation of the cyclin b p34cdc2 complex
MED 95079434:
actions: binding;
Proteins: c Myb; string;
a partial length a myb complementary dna recently cloned by low stringency
hybridization with a c myb probe to complementary dna libraries derived
from human cell lines showed a high degree of homology with the dna binding
domain of c myb and b myb, suggesting that a myb also encoded a dna binding
protein
MED 95098008:
actions: binding; suppress;
Proteins: cyclin A; E2F;
the rb related p107 protein can suppress e2f function independently of
binding to cyclin a cdk2
MED 95107265:
actions: suppress;
Proteins: wee1; DEAD box RNA helicase;
a drosophila gene encoding a dead box rna helicase can suppress loss of
wee1 mik1 function in schizosaccharomyces pombe
MED 95140412:
actions: binding; phosphorylation;
Proteins: cyclin A; cdk2; E2F;
the binding of e2f 1 to e2 promoter was found to be reduced by
phosphorylation of e2f 1 by cyclin a cdk2, suggesting that phosphorylation
of e2f 1 may induce shut off of gene expression at the transcriptional level
MED 95140412:
actions: modulate; phosphorylated; phosphorylation;
Proteins: cyclin A; cdk2; E2F;
these results suggest that e2f 1 is phosphorylated by cyclin a cdk2 in the
s phase in vivo as well as in vitro and that its phosphorylation by cyclin
a cdk2 may modulate its activity.
MED 95140412:
actions: phosphorylated;
Proteins: E2F; cyclin D;
cyclin d1 cdk4 phosphorylated prb but scarcely phosphorylated gst e2f 1 or
h1 histone
MED 95140412:
actions: phosphorylated;
Proteins: cyclin A; cdk2; E2F; cyclin E;
gst e2f 1 was phosphorylated by cyclin a cdk2 more efficiently than by
cyclin e cdk2
MED 95140412:
actions: phosphorylated;
Proteins: cyclin A; cdk2; E2F;
e2f 1 was prepared by immunoprecipitation with anti e2f 1 antibody from
imr32 lysates and was effectively phosphorylated by human cyclin a cdk2
which was expressed in insect cells using baculovirus system
MED 95140412:
actions: phosphorylated;
Proteins: cyclin A; cdk2; E2F;
phospho peptide mapping indicated that its cleavage profile was identical
with that of e2f 1 phosphorylated by cyclin a cdk2 in vitro
MED 95140412:
actions: phosphorylation;
Proteins: E2F; cyclin D;
transcription factor e2f 1 has a putative consensus sequence for
phosphorylation by cyclin dependent kinase
MED 95143663:
actions: inhibited; phosphorylation;
Proteins: p34cdc2; cyclin B;
in cells of higher eukaryotic organisms the activity of the p34cdc2 cyclin
b complex is inhibited by phosphorylation of p34cdc2 at two sites within
its amino terminus
MED 95170107:
actions: binding; interact;
Proteins: DP; E2F;
x1 dp 1, which is highly conserved with murine dp 1, is a major dna binding
component of x1 drtf1 e2f. both dp 1 and dp 2 synergistically interact with
members of the e2f family of proteins, e2f 1, e2f 2, and e2f 3, to generate
dna binding complexes that specifically recognize the e2f site and
functionally interact with e2f 1 in e2f site dependent transcriptional
activation of cellular genes
MED 95188985:
actions: associated with; binding; phosphorylation;
Proteins: cyclin B; cdc2;
oocyte maturation is triggered by the activation in the oocyte cytoplasm of
maturation promoting factor, which consists of cdc2 and cyclin b. immature
goldfish oocytes contain only inactive monomeric 35 kda cdc2 and do not
stockpile cyclin b. in maturing oocytes, activation of cdc2 is associated
with its thr161 phosphorylation and mobility shift on sds page from 35 to
34 kda after binding to cyclin b. using mutant cdc2, we show that thr161
phosphorylation is required for both the downward shift and the kinase
activation
MED 95188985:
actions: binding; phosphorylated;
Proteins: cyclin B; cdc2;
since cdc2 tyr15 is not phosphorylated after binding to cyclin b, it does
not require dephosphorylation
MED 95249267:
actions: regulation; target;
Proteins: DP; E2F;
moreover, an analysis of a dominant negative and mutant dp 1 proteins
suggests that the primary target through which dp 1 mediates its oncogenic
activity is unlikely to be due to the regulation of e2f site
transcription, suggesting an e2f independent effector function for dp 1
MED 95252806:
actions: activated;
Proteins: PCNA; DP; E2F;
expression of the e2f 1 dp 1 heterodimer activated the cat gene with the
pcna intron
MED 95252806:
actions: binding;
Proteins: PCNA; DP; E2F;
this pcna intron region contains a binding site recognized by the
transcription factor e2f. to test whether this site is functional, we
cotransfected pcna cat genes with e2f 1 and dp 1 expression plasmids
MED 95253012:
actions: phosphorylation; regulates;
Proteins: p34cdc2; mpf; cyclin B;
our results indicate that in xenopus oocytes, the pka pathway negatively
regulates the activation of mpf and the activity of p34cdc2 cyclin b
complex through tyrosine phosphorylation of p34cdc2 during metaphase i.
MED 95268146:
actions: phosphorylates;
Proteins: wee1; cdc2; cyclin D;
the recombinant xenopus wee1 protein efficiently phosphorylates cdc2
exclusively on tyr 15 in a cyclin dependent manner
MED 95268146:
actions: phosphorylates;
Proteins: wee1; cdc2;
the interphase, underphosphorylated form of wee1 phosphorylates cdc2 very
efficiently, whereas the mitotic, hyperphosphorylated version is weakly
active as a cdc2 specific tyrosine kinase
MED 95273084:
actions: associated with; phosphorylated;
Proteins: cyclin A; cdk2; E2F;
we confirmed that unphosphorylated prb associated with various types of e2f
but prb has been phosphorylated by cyclin a cdk2 did not
MED 95273084:
actions: phosphorylation;
Proteins: cyclin A; E2F;
we also found that not only the e2f prb complexes but also the e2f p107
complexes were disrupted upon phosphorylation by cyclin a cdk2
MED 95273084:
actions: phosphorylation;
Proteins: cyclin A; cdk2; E2F; cyclin D; cyclin E;
furthermore, e2f prb complexes were disrupted through phosphorylation by
cyclin d1 cdk4 and cyclin e cdk2, as well as by cyclin a cdk2
MED 95273084:
actions: phosphorylation;
Proteins: cyclin A; cdk2; E2F;
we found that e2f prb complexes were disrupted as a consequence of
phosphorylation by cyclin a cdk2, and the levels of the free forms of e2fs
increased
MED 95273084:
actions: phosphorylation; regulated;
Proteins: E2F; cyclin D;
the interactions of e2f with prb and with p107 are regulated via the
phosphorylation of prb and p107 by a cyclin dependent kinase
MED 95273084:
actions: phosphorylation; regulates;
Proteins: E2F; cdks;
these results clearly demonstrate that the phosphorylation of prb and p107
by cdks regulates the formation of complexes between e2f and prb or p107.
MED 95273084:
actions: phosphorylation; regulation;
Proteins: E2F; cyclin D;
it has been postulated that the product of the retinoblastoma gene
dissociates from the e2f prb complex upon phosphorylation by cyclin
dependent kinase s . however, there is no direct evident for the regulation
of formation of the e2f prb complex via phosphorylation by purified cdk
MED 95273100:
actions: activate;
Proteins: myc; DP; E2F;
finally, we found that sp1 and e2f 1 dp 1 cooperatively trans activate c
myc promoter
MED 95279959:
actions: binding; phosphorylation; regulated;
Proteins: wee1; cdc2;
throughout most of the cell cycle and until the cell is prepared to enter
mitosis, cdc2 kinase activity is negatively regulated by phosphorylation of
a residue within its adenosine triphosphate binding domain by wee1, a
nuclear kinase that maintains mitotic timing in eukaryotic cells
MED 95280906:
actions: binds; binds to;
Proteins: DP; E2F;
e2f 5 resembles the other e2fs in that it binds to a consensus e2f site in
a cooperative fashion with dp 1
MED 95292956:
actions: phosphorylates;
Proteins: wee1; cdc2;
antibody depletion experiments demonstrate that wee1 accounts for most of
the activity that phosphorylates cdc2 on tyr15 in an in vitro assay of hela
cell lysates, hence it is likely to have an important role in the mitotic
control of human cells
MED 95292956:
actions: phosphorylation; regulates;
Proteins: cyclin B; wee1 kinase; cdc2;
wee1 kinase negatively regulates entry into mitosis by catalyzing the
inhibitory tyrosine phosphorylation of cdc2 cyclin b kinase. we report here
an investigation of human wee1
MED 95303468:
actions: regulated;
Proteins: cdc2; E2F;
e2f p130 complexes are present only in quiescent l1 cells and disappear at
the g1 s phase boundary concomitantly to induction of dna synthesis and
expression of the e2f regulated cdc2 gene
MED 95303513:
actions: binds;
Proteins: gadd45; PCNA;
using a peptide elisa approach, we showed that gadd45 protein binds
strongly to three regions of pcna and weakly to residues 121 170
MED 95306856:
actions: phosphorylated; phosphorylation;
Proteins: cyclin B; cdc2;
however, at threshold concentrations, a cdc2 cyclin b complex containing a
mutant cdc2 subunit that cannot be phosphorylated on either tyrosine 15 or
threonine 14 displays a markedly reduced capacity to induce mitosis in the
presence of aphidicolin. this observation indicates that the replication
checkpoint in xenopus egg extracts functions without the inhibitory
tyrosine and threonine phosphorylation of cdc2
MED 95306857:
actions: activate; phosphorylate;
Proteins: cdk2; cdc2;
these findings implicate a kinase other than cdc2 and cdk2 that may
initially activate cdc25 in vivo and suggest that this kinase may also
phosphorylate m phase substrates even in the absence of cdc2 kinase.
MED 95315058:
actions: binding;
Proteins: myc; E2F;
in this study, we assessed the changes of the e2f binding pattern to the p2
promoter region of the c myc gene during differentiation into both lineages
MED 95315058:
actions: binding;
Proteins: myc; E2F;
the effects of the anti c myc antibody and the recombinant c myc protein
on the e2f binding patterns suggest that the c myc protein is not involved
directly in these changes
MED 95317603:
actions: regulated;
Proteins: dmcyce; cyclin E;
moreover, dmcyce expression in endoreduplicating cells is down regulated by
ectopic expression of a heat inducible cyclin e transgene
MED 95324807:
actions: activate;
Proteins: E2F; cyclin E; thus, this tissue specific e2f independent transcription of cyclin e reverses the hierarchical relationship between cyclin e and e2f. both hierarchies activate expression of the full complement of replication functions controlled by e2f;
however, whereas inactivation of e2f can produce a g1 when cyclin e is
downstream of e2f, we propose that an e2f independent source of e
eliminates g1.
MED 95324807:
actions: activates;
Proteins: E2F; cyclin E;
the rapidly proliferating cns cells, which exhibit no obvious g1, express
cyclin e constitutively and independently to e2f. instead, cyclin e
expression activates e2f in the cns
MED 95324807:
actions: target;
Proteins: E2F; cyclin E;
cyclin eis a limiting downstream target of e2f. the e2f transcription
factor is required for s phase in drosophila
MED 95337108:
actions: binding;
Proteins: PCNA; p21;
we provide evidence that p21 first inhibits the replication factor c
catalyzed loading of pcna onto dna and second prevents the binding of dna
polymerase delta core to the pcna clamp assembled on dna
MED 95347583:
actions: regulate; regulated;
Proteins: cdk2; E2F;
p107 uses a p21cip1 related domain to bind cyclin cdk2 and regulate
interactions with e2f. the kinase activities of the cyclin cdk complexes
can be regulated in a number of ways
MED 95352847:
actions: phosphorylation;
Proteins: wee1; cdc2;
here, we demonstrate that wee1 overexpression leads to a high stoichiometry
of phosphorylation at a previously undetected site in s. pombe cdc2, t14
MED 95354769:
actions: phosphorylation;
Proteins: p34cdc2; cyclin B; cyclin B2;
altogether, our results show that the accumulation of inactive p34cdc2
cyclin b2 during the long lasting prophase of the oocyte is positively
controlled by pp2a through the tyrosine phosphorylation of p34cdc2.
MED 95354769:
actions: phosphorylation; regulated;
Proteins: Protein phosphatase 2A; p34cdc2;
tyrosine phosphorylation of p34cdc2 is regulated by protein phosphatase 2a
in growing immature xenopus oocytes
MED 95403582:
actions: activated; phosphorylation;
Proteins: cyclin B; wee1 kinase; cdc2;
wee1 kinase dependent phosphorylation of cdc2 maintains the cdc2 cyclin b
complex in an inert form until it is activated by the cdc25 tyrosine
phosphatase at the end of g2
MED 95403582:
actions: regulation;
Proteins: wee1; cdc2;
as described for cdc25, cell cycle linked changes in the intracellular
localisation of wee1 may constitute an important aspect of the temporal
regulation of cdc2 activity
MED 96008579:
actions: phosphorylate;
Proteins: wee1; cdc2;
a complementary dna was cloned from xenopus that encodes myt1, a member of
the wee1 family that was discovered to phosphorylate cdc2 efficiently on
both threonine 14 and tyrosine 15
MED 96027622:
actions: regulation;
Proteins: PCNA; E2F;
these results demonstrate, for the first time, an essential role for e2f
sites in regulation of pcna promoter activity during development of a
multicellular organism.
MED 96027622:
actions: regulation;
Proteins: Proliferating cell nuclear antigen; E2F;
essential role of e2f recognition sites in regulation of the proliferating
cell nuclear antigen gene promoter during drosophila development
MED 96027622:
actions: target;
Proteins: PCNA; E2F;
these results indicate that the pcna gene is a likely target gene of e2f.
examination of lacz expression from pcna lacz fusion genes carrying
mutations in either or both of two e2f sites introduced into flies by germ
line transformation revealed that site ii plays a major role in the pcna
promoter activity during embryogenesis and larval development, although
both sites are required for optimal promoter activity
MED 96028438:
actions: phosphorylation;
Proteins: cyclin B; wee1 kinase; cdc2;
furthermore, the activity of the wee1 kinase was reduced by phosphorylation
with the mitotic extract which contained cdc2 cyclin b kinase.
MED 96038871:
actions: binding;
Proteins: DP; E2F;
the dp 3 proteins studied can co operate with e2f 1 in dna binding activity
and trans activation of e2f site dependent transcription
MED 96038885:
actions: binding; binds; binds to; interact; interaction;
Proteins: p21; cyclin B; cyclin D; cdks;
using a simple in vitro binding assay, we show that p21cdkn1 and the
related p27kip1 can efficiently interact with cyclins d1, d2, d3, e and a,
and to a lesser extent with cyclin b. by generating a deleted form of
cyclin d1 that binds to p21 and p27 but not to cdks, we confirm that these
interaction do not depend on stoichiometric amounts of the relevant kinase
subunit
MED 96069396:
actions: binding; modulate;
Proteins: DP; E2F;
the e2f dna binding activity consists of a heterodimer between e2f and dp
family proteins, and these interactions are required for association of e2f
proteins with prb and the prb related proteins p107 and p130, which
modulate e2f transcriptional activities
MED 96069400:
actions: interact; interacts;
Proteins: cdc2; E2F;
the 20 element of the cdc2 gene specifically interacts with a subset of
e2f 4 p130 complexes present in g0 cells but does not interact with s phase
specific e2f complexes
MED 96087653:
actions: binding; interact; regulated;
Proteins: DP; E2F;
we show that a drosophila dp protein which can interact co operatively with
e2f proteins is a physiological dna binding component of drosophila drtf1
e2f. an analysis of the expression patterns of a drosophila dp and e2f
protein indicated that dmdp is developmentally regulated and in later
embryonic stages preferentially expressed in proliferating cells
MED 96087653:
actions: binding; interacts;
Proteins: DP; E2F;
in mammalian cells drtf1 e2f is a heterodimeric dna binding activity which
arises when a dp protein interacts with an e2f protein
MED 96109222:
actions: activated; binding;
Proteins: E2F; cyclin D; cyclin E;
e2f binding sites are found in both the cyclin e and cyclin d1 promoters,
both promoters are activated by e2f gene products, and at least for cyclin
e, the e2f sites contribute to cell cycle dependent control
MED 96109222:
actions: regulated;
Proteins: G1 Cyclin; E2F;
in addition, e2f activity appears to be directly regulated by the action of
retinoblastoma protein and rb related proteins and indirectly regulated
through the action of g1 cyclins and associated kinases
MED 96117048:
actions: phosphorylates;
Proteins: wee1 kinase; cdc2;
drosophila wee1 kinase rescues fission yeast from mitotic catastrophe and
phosphorylates drosophila cdc2 in vitro
MED 96122901:
actions: activated;
Proteins: cdc2; twine;
the same phenotype was also observed in twine and twine, dmcdc2ts double
mutant testes, consistent with the idea that the cdc2 kinase activity
required for meiotic divisions is activated by the twine cdc25 phosphatase
MED 96128119:
actions: binding;
Proteins: cyclin A; E2F;
here, we show that suppression of e2f 1 dna binding activity by cyclin a
kinase is linked to orderly s phase progression
MED 96128119:
actions: binding; regulation;
Proteins: cyclin A; E2F;
cyclin a kinase regulation of e2f 1 dna binding function underlies
suppression of an s phase checkpoint
MED 96132868:
actions: binding;
Proteins: PCNA; E2F;
our results demonstrate that the e2f like sequence and the protein s
binding to it are required for optimal pcna promoter activity and il 2
induction of pcna expression.
MED 96132868:
actions: binding;
Proteins: PCNA; E2F;
the sequence 5' ttgcgggc 3' located at +10 to +17 is similar to the e2f
consensus binding site and is required for optimal pcna promoter activity
MED 96152368:
actions: phosphorylation;
Proteins: cdk2; cyclin E;
the lack of cyclin e cdk2 activity in suspended cells appeared to result
from increased expression of cdk2 inhibitors and a concomitant decrease in
phosphorylation of cdk2 on threonine 160
MED 96183919:
actions: activate; binding;
Proteins: cyclin A; E2F;
we demonstrate that p107 represses the cyclin a promoter through its cell
cycle regulatory e2f binding site and that 12s e1a can activate the cyclin
a promoter, essentially by counteracting its repression by p107
MED 96187863:
actions: associated with;
Proteins: cyclin B; cdc2; cyclin B2;
the activity of cdc2 closely paralleled the accumulation of cyclin b2, but
cell cycle acceleration caused by cyclin b overexpression was not
associated with elevation of cdc2 activity to higher than metaphase levels
MED 96187863:
actions: phosphorylated;
Proteins: cyclin B; cdc2;
cyclin b1 cdc2 kinase activity oscillated, peaking before each cleavage,
and cdc25c alternated between a highly phosphorylated and a less
phosphorylated form that correlated with high and low cyclin b1 cdc2 kinase
activity, respectively
MED 96187863:
actions: phosphorylation; regulated;
Proteins: cyclin A; cyclin B; cdc2;
although the length of the first embryonic cycle is regulated by both the
level of cyclin b and the phosphorylation state of cdc2, cyclin
accumulation alone was rate limiting for later cycles, since overexpression
of a mitotic cyclin after the first cycle caused cell cycle acceleration
MED 96187863:
actions: phosphorylation; regulation;
Proteins: G1 Cyclin; cdc2; cyclin E;
our results suggest that the timing of the cell cycle in the xenopus embryo
evolves from regulation by accumulation of mitotic cyclins to mechanisms
involving periodic g1 cyclin expression and inhibitory tyrosine
phosphorylation of cdc2.
MED 96210646:
actions: associated with;
Proteins: E2F; cyclin D;
inhibition of cyclin d cdk4 cdk6 activity is associated with an e2f
mediated induction of cyclin kinase inhibitor activity
MED 96215443:
actions: activated;
Proteins: cdk2; cyclin D; cyclin E;
moreover, the cdk2 cyclin d1 complex was not activated by incubation with
cdk4 or cyclin e. thus, cdk2 and cyclin d1 formed a stable complex that was
not activated
MED 96215443:
actions: activated; binding;
Proteins: cdk2; cyclin D;
however, it is not clear whether cdk2 cyclin d1 has unknown targets and why
cdk2 is not activated by binding with cyclin d1
MED 96215443:
actions: activated; phosphorylated;
Proteins: cyclin h; Cdk7; cdk2; cyclin D;
these results strongly suggest that cdk2 forms a stable complex with cyclin
d1 but is not activated because the cdk2 molecule in the complex is not
phosphorylated by cdk7 cyclin h and the phosphorylated cdk2, an active
form, does not bind to cyclin d1.
MED 96215443:
actions: associated with; phosphorylated;
Proteins: cyclin h; Cdk7; cdk2; cyclin D;
cyclin dependent kinase 2 forms an inactive complex with cyclin d1 since
cdk2 associated with cyclin d1 is not phosphorylated by cdk7 cyclin h.
cyclin dependent kinases form complexes with cyclins, and as a consequence
they generally express kinase activities
MED 96215443:
actions: phosphorylated;
Proteins: cyclin h; Cdk7; cdk2; cyclin D; cyclin E;
moreover, we found that cdk2 bound to cyclin d1 was not phosphorylated by
cdk7 cyclin h, while cdk2 bound to cyclin e, as well as free cdk2, was was
phosphorylated by cdk7 cyclin h. additionally, cdk2 phosphorylated by cdk7
cyclin h did not bind to cyclin d1
MED 96217922:
actions: activates;
Proteins: E2F; cyclin E;
whereas the ectopic expression of cyclin e activates de2f dependent
transcription, it has been proposed that cyclin e does not act directly on
de2f but targets a negative regulator of e2f activity
MED 96217922:
actions: interacts; regulates;
Proteins: E2F; cyclin E;
rbf, a novel rb related gene that regulates e2f activity and interacts with
cyclin e in drosophila
MED 96217922:
actions: phosphorylated; regulated;
Proteins: RBF; E2F; cyclin E;
rbf was phosphorylated by a cyclin e associated kinase in vitro, and loss
of function cyclin e mutations enhanced an rbf overexpression phenotype,
consistent with the idea that the biological activity of rbf is negatively
regulated by endogenous cyclin e. the properties of rbf suggest that it is
the intermediary factor that was proposed to allow cyclin e induction of
e2f activity
MED 96220486:
actions: suppressed;
Proteins: p21; E2F;
despite the central role for prb in regulating e2f, p21 suppressed growth
and e2f activity in cells lacking a functional prb
MED 96220486:
actions: target;
Proteins: p21; E2F;
thus, e2f is a critical target and ultimate effector of p21 action, and prb
is not essential for the inhibition of growth or e2f dependent
transcription.
MED 96234309:
actions: activate; binding;
Proteins: twist; bHLH;
inhibition of myogenic bhlh and mef2 transcription factors by the bhlh
protein twist the myogenic basic helix loop helix and mef2 transcription
factors are expressed in the myotome of developing somites and
cooperatively activate skeletal muscle gene expression. the bhlh protein
twist is expressed throughout the epithelial somite and is subsequently
excluded from the myotome. ectopically expressed mouse twist was shown to
inhibit myogenesis by blocking dna binding by myod, by titrating e
proteins, and by inhibiting trans activation by mef2
MED 96240630:
actions: binding;
Proteins: DP; E2F;
e2f dna binding activity in vivo is due to heterodimer formation between
members of the e2f and dp transcription factor families
MED 96251288:
actions: binding;
Proteins: E2F; cyclin E;
an e2f binding site which is required for g1 specific activation of the
cyclin e promoter in synchronized nih 3t3 cells was identified in this
fragment.
MED 96251319:
actions: binding;
Proteins: DP; E2F;
we dissected the functional domains of dp 1 and separated the region that
facilitate heterodimer dna binding from the e2f dimerization domain
MED 96298871:
actions: activate;
Proteins: E2F; cyclin D; cdks;
these data demonstrate that the role of the cyclin d directed cdks in
promoting the progression of cells from g1 into s phase is wholly to
activate an e2f 1 like activity through phosphorylation, thus preventing
the formation of the e2f prb complex
MED 96326307:
actions: phosphorylation;
Proteins: wee1 kinase; cdc2;
and consequent loss of cdc25 phosphatase activity allows inhibitory
phosphorylation of cdc2 by dwee1 kinase, effecting g2 arrest
MED 96338616:
actions: activate;
Proteins: cyclin A; cyclin B; cyclin D;
the results presented here indicate that cyclin a has not lost the ability
to activate its own destruction and that cyclin a mediated activation of
the cyclin destruction pathway permitted destruction of cyclin b1 as well
as cyclin a, indicating that there are not distinct cyclin a and cyclin b
destruction pathways
MED 96338616:
actions: activate;
Proteins: cyclin A; cyclin D;
it has been suggested that the evolutionary recruitment of cyclin a into an
s phase function may have necessitated the loss of an original mitotic
ability to activate the cyclin destruction pathway
MED 96357121:
actions: binding;
Proteins: Myb; DP; E2F;
b myb belongs to a group of cell cycle genes whose transcription is
repressed in g0 early g1 through a binding site for the transcription
factor e2f. here, we show that the b myb repressor element is specifically
recognised by heterodimers consisting of dp 1 and e2f 1, e2f 3 or e2f 4
MED 96357121:
actions: binding; interact;
Proteins: Myb; cyclin A; cdc2; E2F;
surprisingly, e2f mediated repression is dependent on a contiguous
corepressor element that resembles the chr previously established as a
corepressor of the cde in cell cycle genes derepressed in s g2, such as
cyclin a, cdc2 and cdc25c. a factor binding to the b myb chr was
identified in fractionated hela nuclear extract and found to interact with
the minor groove, as previously shown by in vivo footprinting for the
cyclin a chr
MED 96365465:
actions: binding; regulated;
Proteins: ubiquitin; cdk2; cyclin E;
turnover of cyclin e by the ubiquitin proteasome pathway is regulated by
cdk2 binding and cyclin phosphorylation
MED 96365465:
actions: phosphorylation;
Proteins: ubiquitin; cdk2; cyclin E;
binding to cdk2 protects cyclin e from ubiquitination, and this protection
is reversed by cdk2 activity in a process that involves phosphorylation of
cyclin e itself
MED 96374655:
actions: regulation;
Proteins: DP; E2F;
in contrast, coexpression of dp 1 and e2f 1 results in greater loss of g1
regulation and significantly more apoptosis than does e2f 1 alone
MED 96382526:
actions: interacts;
Proteins: cyclin dependent kinase inhibitor; PCNA; Proliferating cell nuclear antigen; cyclin D;
requirement of proliferating cell nuclear antigen in rad6 dependent
postreplicational dna repair. the proliferating cell nuclear antigen acts
as a processivity factor for replicative dna polymerases and is essential
for dna replication. in vitro studies have suggested a role for pcna in the
repair synthesis step of nucleotide excision repair, and pcna interacts
with the cyclin dependent kinase inhibitor p21
MED 96394357:
actions: interaction; phosphorylation;
Proteins: cyclin A; cdk2; cyclin E;
we provide evidence that this differential phosphorylation results from a
specific interaction between hssb p34 and cyclin a, but not cyclin e. thus
the observed cell cycle dependent phosphorylation of hssb p34 at the g1 to
s transition is most likely catalyzed by cyclin a cdk2 initiated by the
direct interaction between cyclin a and the hssb p34 subunit
MED 96413341:
actions: interacts; regulate;
Proteins: DP; E2F;
in vitro p53 interacts with an immunochemically distinct form of dp 1 and
in vivo can regulate transcription driven by the dp 1 e2f 1 heterodimer
MED 96429293:
actions: regulation;
Proteins: DP; E2F;
these results indicate that dp proteins preferentially associate with
specific e2f partners, and suggest that the ability of specific e2f dp
heterodimers to localize in the nucleus contributes to the regulation of
e2f activity.
MED 97000058:
actions: stimulated; target;
Proteins: E2F; cyclin E;
simultaneous overexpression of both drosophila e2f subunits, de2f and ddp,
in embryos stimulated the expression of multiple e2f target genes including
cyclin e, and also caused the initiation of s phase
MED 97006600:
actions: inhibited;
Proteins: p21; E2F;
finally, expression of p21 specifically inhibited transcription from an e2f
dependent promoter but had no effect on a mutant e2 promoter
MED 97127356:
actions: inhibited; phosphorylates;
Proteins: wee1; cdc2;
the m phase induction activity of cdc2 cdc13 is inhibited by wee1 tyrosine
kinase, which phosphorylates cdc2 on tyrosine 15
MED 97127397:
actions: binding;
Proteins: cyclin A; cdk2; E2F; cyclin E;
promoter activation by cyclin e cdk2 requires an e2f binding site in the
cyclin a promoter
MED 97153014:
actions: binding; binds; interact;
Proteins: PCNA; p21;
this species specific response of pcna to p21 cip1 mediated inhibition of
dna synthesis results from a marked difference in the ability of h and s.
cerevisiae pcna to interact with p21 cip1 . as shown by binding studies
using the surface plasmon resonance technique, hpcna binds both full length
p21 cip1 and the p21 cip1 peptide 139 160 stoichiometrically with a
similar affinity while s. cerevisiae pcna binds p21 cip1 with
approximately 10 fold less affinity and does not interact with the p21 cip1
peptide 139 160 .
MED 97153014:
actions: inhibited; interaction;
Proteins: PCNA; p21;
it has recently been shown that in humans, the pcna function, required for
both dna replication and nucleotide excision repair, can be inactivated by
p21 cip1 due to a specific interaction between hpcna and the carboxyl
terminus of p21 cip1 . in this report, we show that saccharomyces
cerevisiae pcna dependent pol delta catalyzed dna synthesis was inhibited
less efficiently than the human system by the intact p21 cip1 protein and
was unaffected by the p21 cip1 carboxyl terminal peptide
MED 97178868:
actions: activates; phosphorylate; phosphorylates;
Proteins: cyclin A; Cdk1; cdk2; cyclin E;
we find that in vitro, cyclin e cdk2 and cyclin a cdk2 phosphorylate
histone h1 similarly but only cyclin a cdk2 phosphorylates lamin b. while
both cyclin a and cyclin e bind cdk1 efficiently, only cyclin a activates
cdk1 kinase activity
MED 97256816:
actions: phosphorylation;
Proteins: p21; cdk2; Cdk activating kinase; cyclin E;
active complexes eluted at a higher molecular weight than inactive
complexes, were relatively deficient in both p21 and p27, and contained
cdk2 with increased threonine 160 phosphorylation, consistent with a
mechanism of activation of cyclin e cdk2 involving both reduced cdk
inhibitor association and cdk activating kinase mediated phosphorylation of
cdk2
MED 97262037:
actions: associated with;
Proteins: p21; cdk2;
ucn 01 further increased luciferase activities in a431 cells transiently
transfected with p21 promoter luciferase reporter plasmid after 24 h
exposure at 260 and 520 nm. ucn 01 also increased the expression of the cdk
inhibitor p27 protein after 24 h exposure at 260 and 520 nm. these results
suggest that g1 phase accumulation induced by ucn 01 is associated with
dephosphorylation of rb and cdk2 proteins as well as induction of cdk
inhibitors p21 and p27.
MED 97312364:
actions: binding;
Proteins: twist; bHLH;
gel mobility shift assays demonstrate that twist can bind to the muscle
creatine kinase e box and inhibit dna binding of heterodimers of e12 with
myogenic bhlh transcription factors like myod. however, a fourfold excess
of twist compared to myod is required for both effects
MED 97315199:
actions: binds; binds to;
Proteins: roughex; cyclin E;
roughex binds to cyclin e and is a substrate for a cyclin e cdk complex in
vitro
MED 97315199:
actions: destabilized;
Proteins: roughex; cyclin A; cyclin E;
in late g1, roughex is destabilized in a cyclin e dependent process,
releasing cyclin a for its role in s g2.
MED 97315199:
actions: regulates;
Proteins: roughex; cyclin A; cyclin E;
whereas roughex inhibits cyclin a accumulation, cyclin e down regulates
roughex protein in vivo
MED 97322239:
actions: activated;
Proteins: cdk2; cyclin D;
therefore, cyclin d2 preferentially activated cdk2 in breast epithelial
cells
MED 97322239:
actions: activates;
Proteins: cdk2; cyclin D;
cyclin d2 activates cdk2 in preference to cdk4 in human breast epithelial
cells
MED 97322239:
actions: inhibited; phosphorylate;
Proteins: cdk2; cyclin D;
the cyclin d2 associated kinase activity was largely inhibited by cdk2
specific inhibitors and could phosphorylate histone h1, a substrate for
cdk2 but not for cdk4 and cdk6
MED 97332618:
actions: phosphorylation;
Proteins: cyclin A; CycE; cdk2; cyclin E;
the induction of cyclin e gene transcription followed by accumulation of
cyclin e mrna in a protein synthesis independent manner and the inhibition
of p27 kip1 association with cyce cdk2 complexes containing newly
synthesised cyce. as a consequence phosphorylation of cyce bound cdk2 by
cyclin activating kinase is accelerated
MED 97336078:
actions: interaction; modulated; regulated;
Proteins: cdk2; cyclin E;
moreover, mutation of t187 in p27 to alanine creates a p27 protein that
causes a g1 block resistant to cyclin e and whose level of expression is
not modulated by cyclin e. a kinetic analysis of the interaction between
p27 and cyclin e cdk2 explains how p27 can be regulated by the same enzyme
it targets for inhibition
MED 97336079:
actions: phosphorylation;
Proteins: DP; E2F; cyclin E;
together with the ability of cyclin e to overcome a g1 block induced by
expression of dominant negative mutant dp 1, a heterodimeric partner of
e2fs, these results provide evidence for a cyclin e controlled s phase
promoting event in somatic cells downstream of or parallel to
phosphorylation of prb and independent of e2f activation
MED 97342624:
actions: binding; phosphorylated; regulated;
Proteins: cyclin A; E2F;
furthermore, heterodimers containing e2f 4, a family member lacking the
cyclin a binding domain found in e2f 1, are not efficiently phosphorylated
or functionally down regulated by cyclin a dependent kinases
MED 97342624:
actions: binding; regulation;
Proteins: cyclin A; DP; E2F;
however, addition of the e2f 1 cyclin a binding domain to e2f 4 conferred
cyclin a dependent kinase mediated down regulation of the e2f 4 dp 1
heterodimer
MED 97342624:
actions: interacts; regulated;
Proteins: cyclin A; E2F;
the transcription factor e2f 1 interacts stably with cyclin a via a small
domain near its amino terminus and is negatively regulated by the cyclin a
dependent kinases
MED 97342624:
actions: phosphorylated;
Proteins: cyclin B; DP; E2F; cyclin D;
using purified components in an in vitro system, we show that the e2f 1 dp
1 heterodimer, the functionally active form of the e2f activity, is not a
substrate for the active cyclin d dependent kinases but is efficiently
phosphorylated by the cyclin b dependent kinases, which do not form stable
complexes with the e2f 1 dp 1 heterodimer
MED 97349071:
actions: binding;
Proteins: cyclin A; cyclin D;
in ves treated bt 20 cells, the cyclin a protein exhibited reduced kinase
activity, which correlated with decreased steady state levels and binding
of cyclin dependent kinase 2 to cyclin a and increased steady state levels
and binding of p21cip1 to cyclin a and cyclin dependent kinase 2
MED 97349071:
actions: binding; phosphorylation;
Proteins: cyclin A; E2F;
ves, although having little effect on e2f 1 steady state protein levels,
decreased e2f 1 phosphorylation and transactivation activity and increased
cyclin a binding to e2f 1
MED 97349071:
actions: binding; regulates;
Proteins: cyclin A; E2F;
increased binding of cyclin a negatively regulates e2f transactivation
activity
MED 97349071:
actions: regulates;
Proteins: cyclin A; E2F;
gal4 e2f 1 deletion mutant studies indicated that cyclin a negatively
regulates e2f function
MED 97349071:
actions: regulation;
Proteins: cyclin A; E2F;
these studies show that ves induces growth inhibition of bt 20 cells
through a mechanism that involves cyclin a negative regulation of e2f
mediated transcription.
MED 97446019:
actions: binding;
Proteins: cdk2; cyclin E;
these findings suggest that the overexpression of cyclin e reverses the p27
kip1 mediated g1 growth arrest by binding the inhibitor restoring the cdk2
associated kinase activity necessary for the g1 s transition
MED 97450983:
actions: binding;
Proteins: cyclin dependent kinase inhibitor; PCNA; p21; cyclin D;
these regions share key hydrophobic residues with the pcna binding domain
of the cyclin dependent kinase inhibitor p21 waf1 cip1 , and all three
competed with one another for binding to pcna
MED 97450983:
actions: binding; binds; binds to;
Proteins: cyclin dependent kinase inhibitor; PCNA; Proliferating cell nuclear antigen; cyclin D;
the dna repair endonuclease xpg binds to proliferating cell nuclear antigen
and shares sequence elements with the pcna binding regions of fen 1 and
cyclin dependent kinase inhibitor p21
MED 97451025:
actions: regulate;
Proteins: PCNA; p21;
a peptide derived from the cell cycle regulator p21 waf1 can disrupt the
mcmt pcna interaction, which suggests that p21 waf1 may regulate
methylation by blocking access of mcmt to pcna
MED 97460716:
actions: phosphorylate;
Proteins: Cdk7; cdk2; cak;
however, the kin28 ccl1 complex does not display cak activity and a
distinct protein kinase able to phosphorylate monomeric cdc28 and gst cdk2
was recently identified, challenging the identification of cdk7 as the
physiological cak in higher eukaryotes
MED 97460716:
actions: suppresses;
Proteins: Cdk7; cak;
here we demonstrate that immunodepletion of cdk7 suppresses cak activity
from cycling xenopus egg extracts, and arrest them before m phase
MED 97467388:
actions: inhibited; target;
Proteins: cyclin A; p21; cdk2; cyclin D;
in contrast to their differential interaction, cyclin a cdk2 and cyclin d2
cdk4 were similarly inhibited by bound p21 cip1 waf1 . roles of cyclin a
cdk2 as a p27 target and cyclin d2 cdk4 as a p27 reservoir may result from
the differential ability of bound p27 to inhibit the kinase subunit in
these complexes.
MED 97477371:
actions: inhibited; phosphorylate;
Proteins: Cdk7; cak;
the ability of cak to phosphorylate the ctd can be inhibited specifically
by a cdk7 pseudosubstrate peptide that also inhibits transcriptional
activation by tat in vitro and in vivo
MED 98001585:
actions: interaction; interacts;
Proteins: twist; bHLH;
although it has been shown that mouse twist sequesters e proteins, thus
preventing formation of myogenic e protein myod complexes and inhibits the
mef2 transcription factor, a cofactor of myogenic bhlh proteins,
overexpression of e proteins and mef2 failed to rescue the inhibitory
effects of m twist on myod. we report here that m twist physically
interacts with the myogenic bhlh proteins in vitro and in vivo and that
this interaction is required for the inhibition of myod by m twist
MED 98005048:
actions: associated with; phosphorylated;
Proteins: cdk2; cyclin E;
on the other hand, serum stimulation of the control r6 cells was associated
with both induction of cyclin e and increased levels of phosphorylated cdk2
proteins and decreased levels of p21waf1 and p27kip1, as the cells
progressed through the g1 phase
MED 98005048:
actions: phosphorylated;
Proteins: cdk2; cyclin D; cyclin E;
thus, even though overexpression of cyclin d1 can induce the expression of
cyclin e and phosphorylated cdk2, premature activation of cyclin e cdk2
kinase activity in quiescent cells or during progression through g1 appears
to be blocked by cdkis
MED 98005048:
actions: phosphorylated;
Proteins: cyclin D; cyclin E;
we found that when compared to r6 control cells, serum starved quiescent r6
ccnd1 cells had not only increased levels of the cyclin d1 protein but
also increased levels of the cyclin e protein. the latter protein was
complexed to phosphorylated cyclin dependent kinase 2
MED 98008107:
actions: associated with;
Proteins: cyclin A; cdk2;
the inhibition of cdk2 activity is associated with a decrease in cyclin a
protein levels, inactivation of cdk2 complexes, and upregulation of p27
kip1 protein.
MED 98026201:
actions: binding;
Proteins: DP; E2F;
glutathione s transferase e2f and gst dp fusion proteins were found to
cooperate in binding to the three e2f sites in the dna polymerase alpha
gene promoter in vitro
MED 98038791:
actions: phosphorylated; phosphorylation;
Proteins: cyclin h; Cdk7; cdk2; cak;
while cdk7 cyclin h is sufficient for phosphorylation of cdk2, we show that
p36mat1 is required for efficient phosphorylation of p53 by cdk7 cyclin h,
suggesting that p36mat1 can act as a substrate specificity determining
factor for cdk7 cyclin h. we have mapped a major site of phosphorylation by
cak to ser 33 of p53 and have demonstrated as well that p53 is
phosphorylated at this site in vivo
MED 98060565:
actions: phosphorylation;
Proteins: myc; cdk2; cyclin E;
cdk2 dependent phosphorylation of p27 facilitates its myc induced release
from cyclin e cdk2 complexes
MED 98070542:
actions: phosphorylated;
Proteins: cyclin A; cdk2; cyclin D; cdks; cyclin E;
cyclin e cdk2 and cyclin a cdk2 phosphorylated a greater number of
substrates than the cyclin d cdks, ranging in size from 10 kda to over 200
kda
MED 98086368:
actions: phosphorylate;
Proteins: cyclin A; cdk2;
in vitro experiments showing that reconstituted gstcyclin a gstcdk2
complexes from phosphorylate recombinant gstp21cip confirms that p21cip is
a cyclin a cdk2 substrate.
MED 98086368:
actions: phosphorylated; phosphorylation;
Proteins: cyclin A; cdk2;
the evidence comes from phosphorylation experiments in which the endogenous
p21cip present in using the original cyclin a cdk2 complexes
immunoprecipitated from hela cells extracts can be phosphorylated by the
cdk2 of the same complexes
MED 98088887:
actions: activate;
Proteins: Myb; cyclin A; cyclin E;
we show that the cell cycle regulators cyclin a and cyclin e activate b myb
by eradicating the inhibition mediated by its carboxy terminus
MED 98118248:
actions: binding;
Proteins: cdk2; cyclin E;
cdk2 alpha and cdk2 beta have very similar binding activity to cyclin e and
to the cdk inhibitor p27kip1
MED 98125536:
actions: activated; binding;
Proteins: DP; E2F;
the expression of a reporter gene containing e2f binding sites in the
promoter is transcriptionally activated by e2f 5 in a cooperative manner
with the dp 1 protein
MED 98158004:
actions: binding;
Proteins: PCNA; rfc;
this process, which is atp dependent, is carried out by 1 recognition of
the primer terminus by rfc binding to and disruption of the pcna trimer,
and then 3 topologically linking the pcna to the dna
MED 98177844:
actions: phosphorylates;
Proteins: wee1; cdc2;
a wee1 type kinase that phosphorylates cdc2 on residue thr14
MED 98187602:
actions: inhibited;
Proteins: cdk2; cyclin D; cyclin E;
ectopic expression of cyclin d1 in progestin inhibited cells led to the
reappearance of the 120 kda active form of cyclin e cdk2 preceding the
resumption of cell cycle progression
MED 98211949:
actions: interaction;
Proteins: cyclin dependent kinase inhibitor; PCNA; p21; cyclin D;
dna polymerase delta, replication factor c, the flap endonuclease fen1, the
cyclin dependent kinase inhibitor p21 and dna ligase i. an inhibition of
dna ligation caused by the interaction of pcna with dna ligase i was found,
and we show that dna ligase i and fen1 can inhibit dna synthesis by dna
polymerase delta pcna
MED 98226760:
actions: phosphorylation;
Proteins: cyclin D; Cdk activating kinase;
the activation of cyclin dependent kinases requires phosphorylation of a
threonine residue within the t loop catalyzed by cdk activating kinases
MED 98252909:
actions: associated with;
Proteins: E2F; cyclin D;
inhibition of cyclin d1 kinase activity is associated with e2f mediated
inhibition of cyclin d1 promoter activity through e2f and sp1
MED 98252909:
actions: inhibited;
Proteins: E2F; cyclin D;
in these studies overexpression of e2f 1 inhibited cyclin d1 dependent
kinase activity, cyclin d1 protein levels, and promoter activity
MED 98252909:
actions: phosphorylation;
Proteins: E2F; cyclin D;
inhibition of cyclin d1 abundance by e2f 1 may contribute to an
autoregulatory feedback loop to reduce prb phosphorylation and e2f 1 levels
in the cell.
MED 98315070:
actions: binding;
Proteins: PCNA; p21;
since sequences similar to the rfts pcna binding motif have been identified
in other dna replication enzymes and in p21 cip1 waf1 , we propose that, in
addition to functioning as a dna polymerase processivity factor, pcna plays
a central role in the recruitment and stable association of dna replication
proteins at replication factories.
MED 98324704:
actions: binding; interacts; regulated;
Proteins: cyclin A; E2F;
in agreement with this conclusion, we find that the cyclin a promoter only
poorly interacts with e2f 4, which is the major e2f family member in g0
cells, while a clear binding is seen with e2f 1 and 3, which are up
regulated in late g1.
MED 98324704:
actions: binding; regulation;
Proteins: cyclin A; E2F;
repression of the cyclin a promoter by cdf 1 and anti repression by e2f.
cell cycle regulation of the cyclin a gene is determined by a bipartite
repressor binding site in the region of the basal promoter, termed cde
chr, which also controls the expression of cell cycle genes upregulated in
s or g2
MED 98336255:
actions: activate;
Proteins: myc; p21; cdk2; cyclin D; cyclin E;
expression of c myc or cyclin d1 was sufficient to activate cyclin e cdk2
by promoting the formation of high molecular weight complexes lacking the
cyclin dependent kinase inhibitor p21, as has been described, following
estrogen treatment
MED 98336255:
actions: binding;
Proteins: myc; p21; cdk2; cyclin D; cyclin E;
these data provide evidence for distinct c myc and cyclin d1 pathways in
estrogen induced mitogenesis which converge on or prior to the formation of
active cyclin e cdk2 p130 complexes and loss of inactive cyclin e cdk2 p21
complexes, indicating a physiologically relevant role for the cyclin e
binding motifs shared by p130 and p21.
MED 98356021:
actions: regulation;
Proteins: cyclin A; dmcyce; cyclin E; string;
in addition, this analysis has identified cyclin a and string as dmcycejp
interactors, suggesting a novel role for cyclin e in the regulation of
cyclin a and string function during eye development.
MED 98368625:
actions: suppresses;
Proteins: DP; E2F;
in addition, overexpression of e2f 6 suppresses the transactivational
effects of coexpression of e2f 1 and dp 1
MED 98403851:
actions: binding;
Proteins: PCNA; rfc; p21;
competition between p21 and pol delta or rfc for binding to pcna results in
efficient inhibition of its stimulation of pol delta dna synthesis and rfc
atpase but not of pcna loading on dna by rfc
MED 98403851:
actions: binding; interact; interaction;
Proteins: PCNA; rfc; p21;
analysis of their functions, along with previously prepared alanine
scanning mutants, demonstrated that some loops interact with dna polymerase
delta and replication factor c. the p21 binding sites of pcna, mapped by
affinity measurement of the mutant forms, found to be located within a
distinct structure of the pcna monomer, overlap with rfc and pol delta
interaction sites
MED 98403851:
actions: interact;
Proteins: PCNA; p21;
functional sites of human pcna which interact with p21, dna polymerase
delta and replication factor c. background
MED 98445358:
actions: associated with;
Proteins: cyclin A; p21; cdk2;
we have found that the kinase activity of cyclin a cdk2 associated with p21
is significantly lower than that of cyclin a cdk2 free of p21, suggesting
that p21 abolishes its activity in vivo, and the use of multiple antibodies
has enabled us to begin the study of the molecular architecture of p21
complexes in vivo
MED 98451282:
actions: binding; stimulates;
Proteins: myc; E2F;
a novel e2f binding protein with myc type hlh motif stimulates e2f
dependent transcription by forming a heterodimer
MED 99027588:
actions: phosphorylation; regulated;
Proteins: E2F; cyclin E;
furthermore, ectopic expression of e2f or the e2f regulated cyclin e gene
promote s phase entry in cells expressing phosphorylation defective prb but
neither is sufficient to trigger completion of s phase
MED 99030287:
actions: interact;
Proteins: dpp; cyclin E;
furthermore, dpp signaling genes interact genetically with a hypomorphic
cyclin e allele
MED 99054678:
actions: activates; interacts;
Proteins: cdk2; cyclin E;
we have isolated a novel human cyclin, cyclin e2, that contains significant
homology to cyclin e. cyclin e2 specifically interacts with cdk inhibitors
of the cip kip family and activates both cdk2 and cdk3
MED 99060131:
actions: phosphorylation; regulation;
Proteins: cyclin B; cdc2;
in the fission yeast schizosaccharomyces pombe and most other species, a
key mode of cdc2 cyclin b regulation is the inhibitory phosphorylation of
cdc2 on tyrosine 15
MED 99077791:
actions: phosphorylation;
Proteins: cdks; Cdk activating kinase;
for full activity, cdks require an activating phosphorylation of a
conserved residue carried out by the cdk activating kinase
MED 99077959:
actions: binding;
Proteins: Proliferating cell nuclear antigen; p21; cdk2; cyclin E;
the kinetics of p21 inhibition of cyclin e cdk2 activity and binding to
proliferating cell nuclear antigen in hct116 p21 + + cells paralleled the
onset of endoreduplication in hct116 p21 cells
MED 99077959:
actions: inhibited;
Proteins: p21; cdk2; cyclin E;
analysis of g1 phase cdk activities demonstrated that the induction of p21
inhibited endoreduplication through direct cyclin e cdk2 regulation
MED 99077959:
actions: regulate;
Proteins: p21; cyclin B; cdc2; cyclin D;
in contrast, loss of p21 did not lead to deregulated cyclin d1 dependent
kinase activities, nor did p21 directly regulate cyclin b1 cdc2 activity
MED 99077959:
actions: regulation;
Proteins: p21; cdk2; cyclin E;
furthermore, we show that mti induced endoreduplication in p53 deficient
hip21 cells was due to levels of p21 protein below a threshold required for
negative regulation of cyclin e cdk2, since ectopic expression of p21
restored cyclin e cdk2 regulation and prevented endoreduplication
MED 99077999:
actions: associated with; inhibited; regulated;
Proteins: p21; cdk2; cyclin E;
the human cyclin e2 gene encodes a 404 amino acid protein that is most
closely related to cyclin e. cyclin e2 associates with cdk2 in a functional
kinase complex that is inhibited by both p27 kip1 and p21 cip1 . the
catalytic activity associated with cyclin e2 complexes is cell cycle
regulated and peaks at the g1 s transition
MED 99077999:
actions: binds;
Proteins: G1 Cyclin; cyclin B; cdk2; cyclin E;
cyclin e2, a novel g1 cyclin that binds cdk2 and is aberrantly expressed in
human cancers a novel cyclin gene was discovered by searching an expressed
sequence tag database with a cyclin box profile
d.) Sentences extracted in the Drosophila cell cycle control example with a simple set of 13 rules about protein function description
cak:
cak is a cdk cyclin complex implicated in the control of multiple cell
cycle transitions.
cak is a trimeric enzyme containing cdk7, cyclin h
cak, a novel cak ercc2 complex, and tfiih
cdc2:
cdc2 an homologue of the product of the gene cdc2 and p45cdc13 or cyclin
an homologue of the product of the gene cdc13
cdc2 and its homologue cdk2
cdc2 belongs to a family of cyclin dependent kinases in higher eukaryotes
cdc2 cyclin b. in xenopus eggs and early embryos a cdc25 homologue
undergoes periodic phosphorylation and activation
cdc2 kinase and a drosophila homologue of the saccharomyces pombe cdc25
tyrosine phosphatase
cdc2 related kinases exists in animal cells, we and others have sought
human homologues of yeast g1 cyclins
cdk2:
cdk2 is a regulator of p27kip1
cdks:
cdks is a substrate oof cyclin a cdk2
dpp:
dpp and the bmp 7 homologue, 60a. decapentaplegic is a transforming
growth factor beta related growth factor that controls multiple
developmental processes in drosophila
dpp is a pathway specific smad, whereas daughters against dpp is an
inhibitory smad genetically shown to antagonize dpp signaling. here
we report the identification of a common mediator smad in
drosophila
dpp is a primary signal in maintaining ubx expression in the visceral
mesoderm in a pattern different from ubx expression in the
embryonic ectoderm and in providing a cell cell communication
mechanism by which ubx expression influences gene expression across
germlayers and across the ps7 to ps8 parasegment boundary in the
visceral mesoderm.
dpp is either bmp 4 or bmp 2, and the homologue os sog is chd. in
xenopus the cns is induced by signals emanating from the organizer,
and two proteins secreted by the organizer, noggin and follistatin,
have been shown to induce neural tissue in animal cap assays. here
we report that chd, another organizer specific secreted factor, has
neuralizing activity and that this activity can be antagonized by
bmp 4
mpf:
mpf is an heterodimer formed of two polypeptides p34cdc2 an homologue of
the product of the gene cdc2 and p45cdc13 or cyclin an homologue of
the product of the gene cdc13
myc:
myc is a 168 amino acid protein with extensive homology to the c myc
amino terminal region, previously shown to contain a
transcriptional activation domain. we hypothesized that b myc might
also function in transcriptional regulation, although its role in
regulating gene expression is predicted to be unique, because b myc
lacks the specific dna binding motif found in other myc proteins.
to determine whether b myc could interact with the transcriptional
machinery
myc is a nuclear phosphoprotein which contains both a leucine zipper and
a helix loop helix dimerization motif
myc is a recently described myc gene whose product has not been
functionally characterized
myc is related to its ability to regulate transcription
p21:
p21 is a membrane associated gtp binding protein
p34cdc2:
p34cdc2 an homologue of the product of the gene cdc2 and p45cdc13 or
cyclin an homologue of the product of the gene cdc13
p34cdc2 and functional homologues from higher eukaryotes.
p34cdc2 dephosphorylation is unknown, but the product of the fission
yeast cdc25+ gene, and its homologues in budding yeast and
drosophila are probably positive regulators of the transition from
g2 to m phase
p34cdc2 is a component of the control mechanism initiating mitosis
generally in eukaryotic cells.
p34cdc2 is a phosphotyrosine protein during the g2 phase of the cell cycle
p34cdc2 kinase activity, we have identified the second site of
phosphorylation as thr167, a residue conserved amongst all p34cdc2
homologues
p34cdc2 protein is entirely absent and is replaced by its human
functional homologue p34cdc2
p34cdc2 proteins, we have constructed a s. pombe strain in which the
yeast cdc2+ gene has been replaced by its drosophila homologue
cdc2dm
roughex:
roughex is a dose dependent regulator of meiosis ii during drosophila
spermatogenesis
string:
string gene is a positive regulator of cdc2 kinase and a drosophila
homologue of the saccharomyces pombe cdc25 tyrosine phosphatase
ubiquitin:
ubiquitin conjugating enzyme ubc 1 is distinct from other rad6
homologues in possessing a c terminal tail 40 amino acid residues
long
ubiquitin is a competitive inhibitor of ubiquitin ethyl ester
hydrolysis. abstract truncated at 250 words
ubiquitin is a small eukaryotic protein that is synthesized naturally as
one of several fusion proteins
wee1:
wee1 kinase is closely related to human and xenopus wee1 homologues, and
can inhibit cdc2 activity by phosphorylating a critical tyrosine
residue
The set of rules:
"protein name" is a ...
"protein name" is related to ...
"protein name" belongs to ...
"protein name", a novel ...
"protein name", a putative ...
"protein name", ...sequence homology to ...
"protein name", a member of the superfamily ...
"protein name", a member of the family ...
"protein name", a new member of ...
"protein name", a novel homologous to ...
"protein name" ...a...homologue...
... like protein "protein name"
isolation of a novel ..., "protein name"