◀ Back to CDKN1A
CDKN1A — E2F1
Pathways - manually collected, often from reviews:
-
BioCarta p53 signaling pathway:
RB/E2F-1 complex (E2F1-RB1)
→
p21 (CDKN1A)
(modification, collaborate)
-
BioCarta p53 signaling pathway:
RB/E2F-1 complex (E2F1-RB1)
→
p21 (CDKN1A)
(modification, collaborate)
-
NCI Pathway Database E2F transcription factor network:
E2F1/DP complex (E2F1-TFDP2_TFDP1)
→
p21CIP1 (CDKN1A)
(transcription, activates)
Gartel et al., Oncogene 1998, Hiyama et al., Oncogene 1997
Evidence: mutant phenotype, physical interaction
-
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
→
E2F1
(reaction)
Connell-Crowley et al., Mol Biol Cell 1997
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
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
Gartel et al., Oncogene 2000
:
A
role for
E2F1 in Ras activation of
p21 ( WAF1/CIP1 ) transcription ... We recently reported that
E2F1 could
transactivate the
p21 promoter via cis acting elements between -119 to +16 bp of the p21 gene ... In contrast, activated Ras was not able to induce the p21 promoter in E2F1-/- fibroblasts, suggesting that
E2F1 is
required for induction of the
p21 promoter by activated Ras ... These data suggest that p53 independent induction of the
p21 promoter by activated Ras is
mediated at least in part by
E2F1
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
Suzuki et al., Int J Cancer 2000
(Mouth Neoplasms...) :
TSA
enhanced the protein expression of
p21 ( WAF1 ), CREB binding protein, cyclinE, cyclin A, Bak and Bax, while it reduced the expression of
E2F-1 , E2F-4, HDAC1, p53 and hyperphosphorylated form of Rb
Park et al., Carcinogenesis 2001
(Prostatic Neoplasms) :
Although expression of E2F-1 was reduced in three prostate cancer cell lines-PC-3, LNCaP and DU-145-the p21 and p27 protein levels were not increased in all the cell lines treated, suggesting that increase in
p21 and p27 protein expression per se is not
responsible for lovastatin mediated down-regulation of
E2F-1
Kuhn et al., Biochim Biophys Acta 2002
:
However, as experiments in p53 deficient cell lines indicated, the decrease of pRb and
E2F-1 is
independent of p53 and
p21 expression
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
Radhakrishnan et al., Oncogene 2004
:
To further elucidate the consequences of
E2F-1 regulated induction of
p21 , we developed cell lines with a tamoxifen dependent form of E2F-1
Harr et al., Molecular cancer 2005
(Carcinoma, Bronchogenic) :
E2F1 , an inducer of cell proliferation, directly
upregulates p73 and in some systems upregulates
p21 directly
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
Russell et al., Oncogene 2006
(Hyperplasia...) :
While Arf inactivation impaired tumor suppression and
p21 induction by
E2F1 , it did not reduce the level of apoptosis observed in E2F1 transgenic mice
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
Latini et al., BMC cancer 2011
(Neoplasms, Experimental...) :
These responses were accompanied by the up-regulation of the cell cycle inhibitor
p21 WAF1 and
reduced ERK phosphorylation and
E2F1 expression
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
Li et al., Cancer Res 1997
(Osteosarcoma) :
Overexpression of
p21waf1 leads to increased inhibition of
E2F-1 phosphorylation and sensitivity to anticancer drugs in retinoblastoma negative human sarcoma cells ... Expression of
p21waf1 reduced cyclin A-associated kinase activity and, surprisingly, resulted in
inhibition of phosphorylation of E2F-1 and increased
E2F-1 binding activity
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