◀ Back to TP53
CDKN2A — TP53
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
TP53
→
Complex of CDKN2A-MDM2
(increases, CDKN2A/MDM2 Activity)
Evidence: CTCF induces expression of the gene encoding p19Arf, which sequesters the p53 inhibitor MDM2, resulting in activation of p53
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Kamijo et al., Proc Natl Acad Sci U S A 1998*
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Stott et al., EMBO J 1998*
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Zhang et al., Mol Cell Biol 2003
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Rizos et al., J Biol Chem 2003*
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Zhang et al., Cell 1998*
-
IRef Biogrid Interaction:
TP53
—
CDKN2A
(physical association, affinity chromatography technology)
Li et al., Clin Cancer Res 2010*
-
IRef Dip Interaction:
TP53
—
CDKN2A
(physical association, coimmunoprecipitation)
Stott et al., EMBO J 1998*
-
IRef Dip Interaction:
TP53
—
CDKN2A
(physical association, coimmunoprecipitation)
Lyakhovich et al., Mol Cell Biol 2003*
-
IRef Intact Interaction:
TP53
—
CDKN2A
(colocalization, fluorescence microscopy)
Kashuba et al., Int J Cancer 2003*
-
IRef Intact Interaction:
Complex of CDKN2A-TP53-ZNF420
(association, anti tag coimmunoprecipitation)
Wang et al., FEBS Lett 2010*
-
IRef Intact Interaction:
Complex of 50 proteins
(association, anti tag coimmunoprecipitation)
Coffill et al., EMBO Rep 2012
Text-mined interactions from Literome
Kurokawa et al., Oncogene 1999
:
Induction of
p19ARF activated
p53 by increasing its stability, and allowed the expression of p21Cip1, which bound to all of the cyclin D1-cdk complexes ( cyclin D1-cdk2, -cdk4, and -cdk6 ) thereby inhibiting their kinase activities
Tao et al., Proc Natl Acad Sci U S A 1999
:
Taken together,
p19(ARF) could
stabilize p53 by inhibiting the nuclear export of Mdm2
Xing et al., Clin Cancer Res 1999
(Carcinoma, Squamous Cell...) :
It was shown that
p14ARF and p16INK4a
play active roles in the
p53 and Rb tumor suppressive pathways, respectively, and p15INK4b is a mediator of the extracellular growth inhibition signals
Khan et al., Proc Natl Acad Sci U S A 2000
(Polyploidy) :
We used p19ARF knockout mouse embryo fibroblasts to show that DNA damage and microtubule disruption
require p19ARF to induce
p53 responses, whereas ribonucleotide depletion and inhibition of RNA synthesis by low doses of actinomycin D do not
Ueda et al., Nihon rinsho. Japanese journal of clinical medicine 2000
(Dysplastic Nevus Syndrome...) :
p16 gene locus also codes for p14ARF and acts as tumor suppressor through
activation of Rb by p16 and
p53 by
p14ARF
Sano et al., Pathol Int 2000
(Carcinoma, Squamous Cell...) :
A physical association between
p14ARF and MDM2 blocks MDM2 induced p53 degradation, resulting in increased
levels of
p53 , which in turn leads to cell cycle arrest
Weitzman et al., Mol Cell 2000
(Hepatitis, Animal) :
Primary fibroblasts lacking JunD displayed
p53 dependent growth arrest, upregulated
p19(Arf) expression, and premature senescence
Querido et al., J Virol 2001
:
Degradation of
p53 was
independent of both MDM2 and
p19ARF , regulators of p53 stability in mammalian cells, but required an extended region of E4orf6 from residues 44 to 274, which appeared to possess three separate biological functions
Raveh et al., Nat Cell Biol 2001
(Cell Transformation, Neoplastic) :
Ectopic expression of DAP kinase suppressed oncogenic transformation of primary embryonic fibroblasts by activating
p53 in a
p19ARF dependent manner
Roper et al., EMBO Rep 2001
(MAP Kinase Signaling System) :
Thus,
p19ARF is not
essential for Raf induced
p53 induction and cell cycle arrest in keratinocytes, indicating that oncogenes engage p53 activity via multiple mechanisms
Esteller et al., Cancer Res 2001
:
Because it is known that
p14ARF prevents MDM2 nucleocytoplasmic shuttling and thus
stabilizes p53 by attenuating MDM2 mediated degradation, we studied the relationship of p14ARF epigenetic silencing to the expression and localization of MDM2 and p53
Lin et al., Proc Natl Acad Sci U S A 2001
(Carcinoma, Squamous Cell...) :
This result suggests that
p19(ARF) can
activate p53 without overtly affecting Mdm2 subcellular localization
Ho et al., Breast Cancer Res Treat 2001
(Breast Neoplasms...) :
p14ARF , an alternate transcript of the INK4A tumor suppressor locus,
prevents hdm2 induced transcriptional silencing of
p53 by binding hdm2
Rizos et al., Oncogene 2001
(Genetic Predisposition to Disease...) :
This mutant
p14ARF , 60ins16, was restricted to the cytoplasm, did not
stabilize p53 and was unable to arrest the growth of a p53 expressing melanoma cell line
Piboonniyom et al., Oral Oncol 2002
(Carcinoma, Squamous Cell...) :
This locus encodes two partially overlapping genes, the cdk inhibitor
p16(ink4a) , and p14(ARF), an
inhibitor of mdm2 mediated degradation of
p53
Ferbeyre et al., Mol Cell Biol 2002
(MAP Kinase Signaling System) :
Although the levels of exogenous p53 achieved in ARF-null cells were relatively low, the stabilizing
effects of
p19(ARF) on
p53 could not explain the cooperation between oncogenic Ras and p53 in promoting senescence
Tsuji et al., Biochem Biophys Res Commun 2002
:
By inactivating Mdm2,
p19(ARF) upregulates
p53 activities to induce cell cycle arrest and sensitize cells to apoptosis in the presence of collateral signals
Rogoff et al., Mol Cell Biol 2002
:
We find that although
p19ARF contributes to
p53 accumulation in response to E2F expression, p19ARF is not required for E2F1 mediated apoptosis
Kuo et al., Cancer Res 2003
:
p19(Arf) induces growth arrest by antagonizing the activity of the p53 negative regulator, Mdm2, thereby
inducing a
p53 transcriptional response
Zhu et al., Chin J Cancer 2003
:
When expression of p53 elevated, p53-mdm2 and
p14(ARF)-mdm2 feedback loops can accurately
regulate the expression level of
p53 , and the cooperation of p33ING1b gene is also needed in the process of p53 exerting normal function
Zhang et al., Chin Med J (Engl) 2003
(Pancreatic Neoplasms) :
Western blotting showed
p14ARF upregulates
p53 expression
Xia et al., Cancer Res 2004
(Breast Neoplasms) :
In summary, these results demonstrate that up-regulation of
p14ARF paralleled with MDM2 inhibition
contributes to
p53 accumulation in the nucleus and causes a high responsiveness of p53 in chronic IR-treated breast cancer cells
Jackson et al., Oncogene 2004
(Bone Neoplasms...) :
We conclude that the phosphorylation of p53 on N-terminal serine residues is not required for increased transcription of the great majority of p53-responsive genes and that the
induction of
p53 by
p14ARF , with little phosphorylation, leads to substantial repression of genes whose products have roles in proliferation
Li et al., Oncogene 2004
(Ataxia Telangiectasia) :
P14/p19ARF ( ARF )
plays a major role in the activation of
p53 by oncogenic signals ... We report here that forced expression of
p14ARF enhances phosphorylation of
p53 serine 15 (p53S15) in NIH3T3, IMR90 and MCF7 cells
Kuo et al., Genes Dev 2004
:
Although
p19Arf binds to the Mdm2 E3 ubiquitin protein ligase to
activate p53 , neither of these molecules regulates p19Arf turnover
Kelly-Spratt et al., PLoS Biol 2004
(Carcinoma, Squamous Cell...) :
Ectopic expression of oncogenes such as Ras induces expression of
p19(Arf) , which, in turn,
activates p53 and growth arrest
Vestey et al., Breast Cancer Res 2004
(Breast Neoplasms...) :
p14ARF is negatively
regulated by
p53 and through p53 independent pathways
Lozano et al., J Pathol 2005
(Disease Models, Animal...) :
Additionally, upstream
regulators of
p53 activity, such as
p19(Arf) and Atm, are themselves critical tumour modifiers/suppressors
Tanaka et al., Nephron. Physiology 2005
(Acute Kidney Injury...) :
We also examined the
effect of
p19(ARF) overexpression on
p53 levels and cell cycle progression in MDCK cells
Silva et al., EMBO J 2005
:
In cultured cells,
p19Arf decreased Pdgfrbeta and
blocked Pdgf-B-driven proliferation independently of Mdm2 and
p53
Warburton et al., Cancer Res 2005
(Carcinoma, Renal Cell...) :
We have found that
p53 is functional in p53 wild-type renal cell carcinoma cells and that this activity is significantly
regulated by MDM2 and to a much lesser extent by
p14ARF
Balsitis et al., J Virol 2005
(Hyperplasia...) :
While E7-mediated p21 induction was partially p53 dependent, neither
p53 nor p21 induction by E7
required p19(ARF)
Castillo et al., J Virol 2005
:
We present here evidence suggesting that IE1-72 may activate the p53 pathway by increasing the levels of
p19(Arf) and by
inducing the phosphorylation of
p53 at Ser15
Ruiz et al., Cell cycle (Georgetown, Tex.) 2006
(Carcinoma, Squamous Cell...) :
In particular, we characterized the aberrant
p53 activation
mediated by
E2F/p19(ARF) and other transduction pathways
Zeini et al., J Immunol 2006
:
This up-regulation of
p19(ARF) activates
p53 , leading to apoptosis
Lara et al., Mol Carcinog 2007
(Carcinoma, Squamous Cell...) :
Detailed biochemical analyses have indicated that, in the absence of pRb, multiple pathways, including the aberrant
p53 activation
mediated by
E2F/p19(ARF) , are activated leading to increased tumor apoptosis
Rizos et al., Cell cycle (Georgetown, Tex.) 2007
(Genetic Predisposition to Disease) :
p14ARF regulates E2F-1 ubiquitination and degradation via a
p53 dependent mechanism
Mascaux et al., Eur Respir J 2008
(Bronchial Neoplasms...) :
Murine double minute clone 2 (MDM2), p14 alternate reading frame
(p14arf) , and nucleophosmin (NPM)
regulate p53 activity
Leong et al., Mol Cancer Res 2009
:
p53 Deficiency
leads to compensatory up-regulation of
p16INK4a ... Here, we report that
p53 controls
p16(INK4a) expression in a unique way ...
p53 deficiency
led to up-regulation of
p16(INK4a) in primary mouse embryonic fibroblasts, osteoblasts, and various mouse organs, and an increase in the p16(INK4a) promoter activity, without affecting the half-life of p16(INK4a) ... Reconstitution of p53, but not mutant
p53 ,
restored the proper expression of
p16(INK4a) ...
p53 did not
repress the
p16(INK4a) promoter activity either
Huschtscha et al., J Cell Sci 2009
:
Exogenous p16(INK4a) expression decreased levels of both p53 transcript and protein, and this effect was inhibited by nutlin-3a, indicating that
p16(INK4a) can
regulate p53 expression by affecting both p53 transcription and Mdm2 dependent degradation of p53
Kashuba et al., Int J Cancer 2011
(Breast Neoplasms) :
This resembles the
effect of
p14ARF on
p53
Kawagishi et al., Cancer Res 2010
(Cell Transformation, Neoplastic...) :
Translational repression of VEGFA mRNA by
p19(ARF) does not
require p53 , a major target of the ARF tumor suppressor pathway, but instead correlates with binding to nucleophosmin/B23
Macias et al., Cancer Cell 2010
:
Furthermore, ribosomal perturbation induced
p53 response does not
require tumor suppressor
p19ARF
Xie et al., Zhongguo Fei Ai Za Zhi 2006
:
Both
p16INK4a and p14ARF are cell cycle regulatory proteins and
play an important role in Rb and
p53 passways respectively
Chien et al., Oncogene 2011
:
Here, we report that, in two p16 ( -/- ), pRb ( WT ) and
p53 ( WT ) cell lines ( MCF7 and U87 ),
p16(INK4a) overexpression
induces a dramatic decrease in CDK1 protein expression
Nakamura et al., Mol Cell Biol 2011
:
In the absence of Hzf and HuR,
p53 induction by
p19(ARF) is significantly attenuated, and the cells consequently acquire resistance to p19(ARF)
Nishizawa et al., Cancer Sci 2012
:
Bach1 mediated suppression of
p53 is
inhibited by
p19(ARF) independently of MDM2
Widau et al., Mol Cell Biol 2012
:
Although
p19(Arf) controls Pdgfrß mRNA in a
p53 dependent manner, it also blunts Pdgfrß protein expression by blocking new protein synthesis in the absence of p53
Yamada et al., Mol Cell 2013
:
p14ARF activates
p53 by binding and inhibiting HDM2, resulting, inter alia, in increased transcription and expression of the cyclin dependent kinase inhibitor p21 and consequent cell-cycle arrest
Nichols et al., Case reports in oncological medicine 2013
:
The primary tumor and blood underwent exome sequencing which revealed deletions in
CDKN2A as well as PPP1R13B, which
induces p53
Parker et al., DNA Cell Biol 1994
(Melanoma...) :
The variation of p53 in association with mts1 gene expression suggests that the
mts1 product might interact with and
stabilize p53