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CCND1 — CDKN2A
Pathways - manually collected, often from reviews:
-
KEGG Cell cycle:
CDKN2A
→
Complex of CCND1-CCND2-CCND3-CDK4-CDK6
(protein-protein, inhibition)
-
KEGG Pathways in cancer:
CDKN2A
→
Complex of CCND1-CDK4-CDK6
(protein-protein, missing interaction)
-
KEGG Glioma:
CDKN2A
→
Complex of CCND1-CDK4-CDK6
(protein-protein, missing interaction)
-
KEGG Melanoma:
CDKN2A
→
Complex of CCND1-CDK4-CDK6
(protein-protein, missing interaction)
-
KEGG Bladder cancer:
CDKN2A
→
Complex of CCND1-CDK4
(protein-protein, missing interaction)
-
KEGG Chronic myeloid leukemia:
CDKN2A
→
Complex of CCND1-CDK4-CDK6
(protein-protein, missing interaction)
-
KEGG Non-small cell lung cancer:
CDKN2A
→
Complex of CCND1-CDK4-CDK6
(protein-protein, missing interaction)
-
NCI Pathway Database Regulation of retinoblastoma protein:
RB1/E2F1-3/DP/HDAC1 complex (RB1-HDAC1-E2F3_E2F2_E2F1-TFDP1)
→
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
(modification, collaborate)
Zhang et al., Cell 2000, Rubin et al., Cell 2005, Kato et al., Genes Dev 1993, Fåhraeus et al., Curr Biol 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
→
HDAC1 (HDAC1)
(modification, inhibits)
Zhang et al., Cell 2000, Rubin et al., Cell 2005, Kato et al., Genes Dev 1993, Fåhraeus et al., Curr Biol 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
→
CDK4-6/Cyclin D complex (CDK6_CDK4-CCND3_CCND2_CCND1)
(modification, inhibits)
Zhang et al., Cell 2000, Rubin et al., Cell 2005, Kato et al., Genes Dev 1993, Fåhraeus et al., Curr Biol 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database C-MYB transcription factor network:
p16INK4a (CDKN2A)
→
CDK6/Cyclin D1 complex (CDK6-CCND1)
(modification, activates)
Lei et al., Blood 2005*
-
NCI Pathway Database Regulation of retinoblastoma protein:
p16INK4a (CDKN2A)
→
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
(modification, collaborate)
Fåhraeus et al., Curr Biol 1996
Evidence: physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
p16INK4a (CDKN2A)
→
CDK4-6/Cyclin D complex (CDK6_CDK4-CCND3_CCND2_CCND1)
(modification, collaborate)
Fåhraeus et al., Curr Biol 1996
Evidence: physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
→
CDK4-6/Cyclin D complex (CDK6_CDK4-CCND3_CCND2_CCND1)
(modification, collaborate)
Fåhraeus et al., Curr Biol 1996
Evidence: physical interaction
-
WikiPathways G1 to S cell cycle control:
CDKN2C/CDKN2B/CDKN2D/CDKN2A
→
CCND1/CCND2/CCND3
(inhibition)
-
WikiPathways Signaling Pathways in Glioblastoma:
CDKN2A/CDKN2C/CDKN2B
→
Complex of CCND1-CCND2-CDK4
(mim-inhibition)
-
WikiPathways Signaling Pathways in Glioblastoma:
CDKN2A/CDKN2C/CDKN2B
→
Complex of CCND1-CCND2-CDK6
(mim-inhibition)
-
WikiPathways Bladder Cancer:
CDKN2A
→
CCND1/CDK4
(inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Bova et al., Clin Cancer Res 1999
(Carcinoma, Squamous Cell...) :
Loss of
p16INK4A in the
presence of
cyclin D1 overexpression conferred a significantly worse disease-free ( P = 0.011 ) and overall ( P = 0.002 ) survival at 5 years
Lee et al., Int J Mol Med 2000
(Glioma) :
p16/INK4a prevents the association of CDK4 with
cyclin D1 , and subsequently inhibits phosphorylation of retinoblastoma tumour suppressor protein ( pRb ), thus preventing exit from the G1 phase
Sugimoto et al., Oncogene 2002
:
This mitogen induced
cyclin D1-kinase activity was
blocked by overexpression of
p16(INK4a) and resulted in the inhibition of S phase entry in p21/p27-null MEFs
Guo et al., Mol Cell Biol 2004
:
We found that ( i ) p19(Arf) or p53 deficiency led to a significant increase in PI 3-kinase activity, which in turn upregulated RhoA and Rac1 activities ; ( ii ) deletion of p19Arf or p53 led to an increase in cell growth rate that was in part dependent on RhoA, Rac1, and Cdc42 activities ; ( iii
) p19(Arf) or p53 deficiency
caused an enhancement of the growth related transcription factor NF-kappa B and
cyclin D1 activities that are partly dependent on RhoA or Cdc42 but not on Rac1 ; ( iv ) forced expression of the activating mutants of Rac1, RhoA, or Cdc42 caused a hyperproliferative phenotype of the p19Arf ( -/- ) and p53 ( -/- ) cells and promoted transformation of both cells ; ( v ) RhoA appeared to contribute to p53 regulated cell proliferation by modulating cell cycle machinery, while hyperactivation of RhoA further suppressed a p53 independent apoptotic signal ; and ( vi ) multiple pathways regulated by RhoA, including that of Rho-kinase, were required for RhoA to fully promote the transformation of p53 ( -/- ) cells
D'Amico et al., Cancer Res 2004
(Breast Neoplasms) :
p16(INK4a) repressed
cyclin D1 expression and transcription ...
Repression of
cyclin D1 by
p16(INK4a) occurred independently of the p16(INK4a)-cdk4 binding function and required a cAMP-response element/activating transcription factor-2 binding site ...
p19(ARF) repressed
cyclin D1 through a novel distal cis-element at -1137, which bound p53 in chromatin-immunoprecipitation assays
Al-Khalaf et al., PloS one 2011
:
p16( INK4a) positively
regulates cyclin D1 and E2F1 through negative control of AUF1 ... Furthermore, AUF1 down-regulation increased the expression levels of these genes, while concurrent silencing of AUF1 and
p16(INK4a) , using specific siRNAs,
restored normal expression of both
cyclinD1 and E2F1
Schulze et al., Oncogene 1994
:
Activation of the E2F transcription factor by
cyclin D1 is
blocked by
p16INK4 , the product of the putative tumor suppressor gene MTS1
Palmero et al., Oncogene 1997
:
In human cells transformed by the large T-antigen of simian virus 40 ( SV40 T-Ag ) and human tumour cell lines that lack a functional retinoblastoma gene product ( pRb ) no
cyclin D1-Cdk4 complexes can be
detected because all the available Cdk4 is associated with the Cdk-inhibitor
p16INK4a
Gill et al., J Clin Invest 1998
:
The level of
p16(INK4a) , an endogenous
inhibitor of the
cyclin D1/cdk4 complex decreased