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CDKN1A — E2F2
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Regulation of retinoblastoma protein:
p21CIP1/CDK2 complex (CDKN1A-CDK2)
→
RB1/E2F1-3/DP complex (RB1-E2F3_E2F2_E2F1-TFDP1)
(modification, inhibits)
Harbour et al., Cell 1999, Chan et al., Nat Cell Biol 2001, Rubin et al., Cell 2005
Evidence: mutant phenotype, assay, reporter gene, physical interaction
-
Reactome Reaction:
CDKN1A
→
E2F2
(reaction)
Connell-Crowley et al., Mol Biol Cell 1997
Text-mined interactions from Literome
Gartel et al., Oncogene 1998
:
In contrast, HBP1 ( HMG-box protein-1 ), a novel retinoblastoma protein binding protein, can repress the
p21 promoter and
inhibit induction of p21 expression by
E2F
Delavaine et al., Oncogene 1999
:
The results suggest that
p21 may
control E2F activity through a pathway that acts independently of pRb
Pruitt et al., J Biol Chem 2000
(Cell Transformation, Neoplastic) :
Conversely, stable expression of activated Raf alone caused only a partial up-regulation of
p21 and Rb hyperphosphorylation but no
activation of
E2F-responsive transcription or down-regulation of p27 in RIE-1 cells
Yamada et al., Proc Natl Acad Sci U S A 2004
:
Interestingly, M44KM64E mutant azurin protein failed to elicit inhibition of cell-cycle progression in MCF-7 cells, presumably because of mutation at the retinoblastoma tumor suppressor protein that allows functional
E2F formation in MCF-7 cells even in the
presence of high intracellular
p21 level
Fandy et al., Neoplasia (New York, N.Y.) 2005
(Multiple Myeloma) :
SAHA and TSA induced G1 phase cell cycle growth arrest by upregulating
p21 ( WAF1 ) and p27 ( Kip1 ) expression and by
inhibiting E2F transcriptional activity
Bock et al., Mol Carcinog 2007
:
Relative non-steroidal anti-inflammatory drug ( NSAID ) antiproliferative activity is mediated through
p21 induced G1 arrest and
E2F inhibition ... Cell cycle analysis showed that celecoxib and sulindac sulfide both induced a 3-fold increase in G ( 1 ) phase distribution, and this correlated with strong induction of
p21 ( waf1/cip1 ), inhibition of cyclin D1, and hypophosphorylation of Rb. Celecoxib and sulindac sulfide treatment
induced strong downstream inhibition of
E2F transactivating activity as determined by a luciferase reporter assay
Chan et al., Mol Cancer Ther 2007
:
Up-regulation of
p21 by CCT129202 in HCT116 cells
led to Rb hypophosphorylation and
E2F inhibition, contributing to a decrease in thymidine kinase 1 transcription
Kim et al., Molecular cancer 2010
(Prostatic Neoplasms) :
These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of
p21 mediated
E2F signaling
Shiyanov et al., Mol Cell Biol 1996
:
Since p21 is believed to be a mediator of p53, we speculated that the
p21 mediated disruption of the cdk2 containing
E2F-p130 complex plays a role in the growth suppression function of p53
Dimri et al., Mol Cell Biol 1996
:
We show that
p21 inhibits the activity of
E2F , an essential growth-stimulatory transcription factor that is negatively regulated by unphosphorylated pRb ...
p21 suppressed the activity of
E2F-responsive promoters ( dihydrofolate reductase and cdc2 ), but E2F-unresponsive promoters ( c-fos and simian virus 40 early ) were unaffected ... Despite the central role for pRb in regulating E2F,
p21 suppressed growth and
E2F activity in cells lacking a functional pRb
Hiyama et al., Oncogene 1998
(Glioma) :
Indeed,
E2F induced levels of
p21 protein during the G1/ S transition is consistent with the recent findings demonstrating that p21 acts as an assembly factor for kinase active cyclin/cdk/p21 complexes
Halaban et al., Oncogene 1998
:
We conclude that neutralization of Rb by E2F1E132, but not the disruption of p16INK4A or
p21WAF1/CIP1 ,
resulted in the accumulation of free
E2F and cell cycle progression