◀ Back to TP53
MDM4 — TP53
Pathways - manually collected, often from reviews:
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Wade et al., Oncogene 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, protein complementation assay)
Wade et al., Oncogene 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Stad et al., J Biol Chem 2000*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Bernal et al., Cancer Cell 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Bernal et al., Cancer Cell 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, protein complementation assay)
Bernal et al., Cancer Cell 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Miller et al., Cell cycle (Georgetown, Tex.) 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Zuckerman et al., J Biol Chem 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, unspecified method)
Kallen et al., J Biol Chem 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(association, x-ray crystallography)
Czarna et al., Cell cycle (Georgetown, Tex.) 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, unspecified method)
Czarna et al., Cell cycle (Georgetown, Tex.) 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(association, x-ray crystallography)
Popowicz et al., Cell cycle (Georgetown, Tex.) 2008*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Hu et al., Cancer Res 2007*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Sharp et al., J Biol Chem 1999*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Li et al., Mol Cell Biol 2002*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Di Conza et al., Cell cycle (Georgetown, Tex.) 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Mancini et al., EMBO J 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Wu et al., Mol Cell Biol 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Shan et al., J Biol Chem 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Wu et al., Mol Cell Biol 2012*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, enzymatic study)
Ranaweera et al., J Biol Chem 2013*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, enzymatic study)
Badciong et al., J Biol Chem 2002*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Shvarts et al., Genomics 1997*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Tang et al., Cell 2008
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Okamoto et al., Mol Cell Biol 2005*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Chen et al., Mol Cell Biol 2005*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Wang et al., FEBS Lett 2001*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(colocalization, imaging technique)
Ohtsubo et al., Cancer Sci 2009*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Zdzalik et al., Cell cycle (Georgetown, Tex.) 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, enzymatic study)
Singh et al., J Biol Chem 2007*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, pull down)
Kim et al., PLoS Comput Biol 2010*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
Li et al., Mol Cell 2011*
-
IRef Biogrid Interaction:
TP53
—
MDM4
(direct interaction, enzymatic study)
David et al., J Biol Chem 2011
-
IRef Biogrid Interaction:
TP53
—
MDM4
(physical association, affinity chromatography technology)
de Graaf et al., J Biol Chem 2003*
-
IRef Dip Interaction:
TP53
—
MDM4
(direct interaction, fluorescence polarization spectroscopy)
Laurie et al., Nature 2006*
-
IRef Dip Interaction:
TP53
—
MDM4
(direct interaction, isothermal titration calorimetry)
Pazgier et al., Proc Natl Acad Sci U S A 2009*
-
IRef Dip Interaction:
TP53
—
MDM4
(direct interaction, affinity chromatography technology)
Wang et al., FEBS Lett 2001*
-
IRef Dip Interaction:
TP53
—
MDM4
(direct interaction, anti bait coimmunoprecipitation)
Laurie et al., Nature 2006*
-
IRef Hprd Interaction:
TP53
—
MDM4
(in vivo)
Parant et al., Nat Genet 2001*, Badciong et al., J Biol Chem 2002*, Li et al., Cancer Res 2004*, Gilkes et al., EMBO J 2006*, Shvarts et al., EMBO J 1996*, Shvarts et al., Genomics 1997*
-
IRef Hprd Interaction:
TP53
—
MDM4
(in vitro)
Parant et al., Nat Genet 2001*, Badciong et al., J Biol Chem 2002*, Li et al., Cancer Res 2004*, Gilkes et al., EMBO J 2006*, Shvarts et al., EMBO J 1996*, Shvarts et al., Genomics 1997*
-
IRef Intact Interaction:
Complex of MDM4-UBA1-TP53-UBE2D2
(ubiquitination reaction, ubiquitinase assay)
Iyappan et al., J Biol Chem 2010*
-
IRef Intact Interaction:
Complex of USP7-TP53-MDM2-MDM4
(association, anti bait coimmunoprecipitation)
Meulmeester et al., Mol Cell 2005*
-
IRef Intact Interaction:
Complex of USP7-MDM4-TP53-USP7-MDM4-TP53
(association, anti bait coimmunoprecipitation)
Meulmeester et al., Mol Cell 2005*
-
IRef Intact Interaction:
Complex of MDM4-TP53-BCL2-TP53-BCL2-MDM4-BCL2-MDM4-TP53
(association, anti bait coimmunoprecipitation)
Mancini et al., EMBO J 2009*
-
IRef Intact Interaction:
TP53
—
MDM4
(physical association, pull down)
Li et al., Cancer Res 2004*
-
IRef Intact Interaction:
TP53
—
MDM4
(physical association, pull down)
Meulmeester et al., Mol Cell 2005*
-
IRef Intact Interaction:
TP53
—
MDM4
(physical association, pull down)
Hu et al., Cancer Res 2007*
-
IRef Intact Interaction:
TP53
—
MDM4
(physical association, enzyme linked immunosorbent assay)
Hu et al., Cancer Res 2007*
-
IRef Intact Interaction:
TP53
—
MDM4
(colocalization, fluorescence microscopy)
Mancini et al., EMBO J 2009*
-
IRef Intact Interaction:
TP53
—
MDM4
(direct interaction, nuclear magnetic resonance)
Sanchez et al., FEBS Lett 2010*
-
IRef Intact Interaction:
TP53
—
MDM4
(direct interaction, isothermal titration calorimetry)
Sanchez et al., FEBS Lett 2010*
-
IRef Intact Interaction:
Complex of MDM4-TP53-MDM2-MDM4-MDM2-TP53
(association, anti tag coimmunoprecipitation)
Hu et al., Cancer Res 2007*
-
IRef Ophid Interaction:
TP53
—
MDM4
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
TP53
—
MDM4
(aggregation, confirmational text mining)
Parant et al., Nat Genet 2001*
Text-mined interactions from Literome
Yu et al., Oncogene 2000
:
In the current study,
MDM2 mediated degradation of
p53 was partially inhibited in cells treated with leptomycin B ( LMB ), a specific inhibitor of nuclear export
Inoue et al., FEBS Lett 2001
:
Importantly,
MDM2 overexpression
inhibited the stabilization of
p53 and decrease in ubiquitination following MMC, MMS, and UV treatment
Gu et al., Blood 2002
(Precursor Cell Lymphoblastic Leukemia-Lymphoma) :
In the presence of wild-type ( wt )
p53 ,
MDM2 increased p65 promoter activity by reversing p53 mediated suppression of p65 ... In the absence of
p53 ,
MDM2 directly
increased p65 promoter activity
Jin et al., J Biol Chem 2002
:
Consistent with the above results,
MDM2 significantly
repressed the activation of
p53 transcriptional activity by PCAF without apparently affecting the level of p53
Wei et al., J Biol Chem 2003
(Osteosarcoma) :
In contrast,
MDM2 inhibits
p53 by promoting its degradation
Ko et al., Oncogene 2003
(Cell Transformation, Neoplastic...) :
In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of
p53 induced p21 ( WAF1 ),
MDM2 , and bax
Mancini et al., J Biol Chem 2004
:
MDM4 ( MDMX ) overexpression
enhances stabilization of stress induced
p53 and promotes apoptosis
Zhao et al., J Biol Chem 2004
:
Interestingly, whereas Daxx did not bind to p53 in cells as assessed by immunoprecipitation,
MDM2 expression
restored p53-Daxx interaction, and this correlated with deacetylation of p53
Li et al., Cancer Res 2004
:
E1A preferentially bound to Mdm4 rather than Mdm2 and formed a complex with
p53 in the
presence of
Mdm4 , resulting in the stabilization of p53 in a p14(ARF) independent manner
Lin et al., Oncogene 2005
(Bone Neoplasms...) :
Overexpressed myc tagged topors associates with and stabilizes p53, and enhances the
p53 dependent transcriptional activities of p21 ( Waf1 ),
MDM2 and Bax promoters and elevates endogenous p21 ( Waf1 ) mRNA levels
Wiederschain et al., J Biol Chem 2005
(Translocation, Genetic) :
Our data show that MLL-AF9, MLL-AF10, MLL-ENL, and MLL-ELL substantially down-regulate
p53 mediated
induction of p21,
MDM2 , and Bax in response to DNA damage
Wang et al., EMBO J 2005
:
Therefore,
MDM2 interaction with KAP1
contributes to
p53 functional regulation
Xiong et al., Proc Natl Acad Sci U S A 2006
:
Synergistic
roles of Mdm2 and
Mdm4 for
p53 inhibition in central nervous system development
Francoz et al., Proc Natl Acad Sci U S A 2006
:
Although Mdm2 prevents accumulation of the p53 protein,
Mdm4 contributes to the overall inhibition of
p53 activity independent of Mdm2 ... We propose a model in which Mdm2 is critical for the regulation of
p53 levels and
Mdm4 is
critical for the fine tuning of p53 transcriptional activity, both proteins acting synergistically to keep p53 in check
Toledo et al., Cancer Cell 2006
(Neoplasms) :
The mechanisms by which Mdm2 and
Mdm4 ( MdmX )
regulate p53 remain controversial ...
Mdm4 loss did not alter Mdm2 stability but significantly
increased p53DeltaP transactivation to partially restore cycle control ... Thus,
Mdm4 regulates
p53 activity, while Mdm2 mainly controls p53 stability
Boesten et al., Cell Death Differ 2006
:
During embryonic development, Mdm2 and
Mdm4 inhibit the growth suppressive activities of
p53 ... Together, Mdm2, but not
Mdm4 ,
prevents accumulation of active
p53 in quiescent SMCs and thereby the induction of p53 mediated caspase-3 independent cell death
Maetens et al., Blood 2007
:
Thus, in this particular cellular context,
Mdm4 only
contributes to
p53 regulation at a specific phase of the differentiation program
Toledo et al., Int J Biochem Cell Biol 2007
(Neoplasms) :
We now know that MDM2 and
MDM4 inhibit
p53 in distinct and complementary ways : MDM4 regulates p53 activity, while MDM2 mainly regulates p53 stability ... We now know that MDM2 and MDM4 inhibit p53 in distinct and complementary ways
: MDM4 regulates
p53 activity, while MDM2 mainly regulates p53 stability
Terzian et al., Mol Cell Biol 2007
(Cell Transformation, Neoplastic...) :
Here we show that Mdm2 and
Mdm4 haploinsufficiency
leads to increased
p53 activity, exhibited as increased sensitivity to DNA damage and decreased transformation potential
Xiong et al., Circulation 2007
(Cardiomyopathy, Dilated) :
Mdm4 , a homolog of Mdm2,
inhibits p53 activity in numerous cell types ... It is unknown whether
Mdm4 plays a role in the inhibition of
p53 in fully differentiated tissues such as adult cardiomyocytes and whether this role is associated with DCM ... Activity of
p53 was
inhibited by
Mdm4 even in the fully differentiated cardiomyocyte
Phang et al., Eur J Cancer 2008
(Leukemia) :
Although mutations in p53 are rare in leukaemia,
MDM2 , the negative
regulator of
p53 , is often overexpressed
Barboza et al., Mol Cancer Res 2008
(Neoplasms, Experimental) :
Mdm2 and
Mdm4 loss
regulates distinct
p53 activities ... These data further differentiate the
roles of Mdm2 and
Mdm4 in the regulation of
p53 activities
Sanchez et al., FEBS Lett 2010
:
MDM2 and
MDM4 are proteins
involved in regulating the tumour suppressor
p53
Markey et al., Frontiers in bioscience (Landmark edition) 2011
(Neoplasms) :
Under normal growth conditions,
MDM4 contributes to the repression of
p53 activity
Yu et al., Cancer 2012
(Carcinoma, Squamous Cell...) :
Given the
roles of both
MDM4 and HPV16 E6 oncoproteins in inhibition of
p53 activity, we tested the hypothesis that MDM4 polymorphisms are associated with the risk of HPV16 associated squamous cell carcinoma of head and neck ( SCCHN )
Di Conza et al., Cell cycle (Georgetown, Tex.) 2012
:
MDM4 enhances
p53 stability by promoting an active conformation of the protein upon DNA damage
Vaughan et al., Genes & cancer 2011
:
Consistently, analysis of functional domains of MDM2 indicated that although the p53-interaction domain of MDM2 contributes to the up-regulation of the NF?B2 promoter,
MDM2 does not
require direct interactions with
p53 for this function
Zhang et al., J Pathol 2012
(Heart Defects, Congenital) :
Synergistic
regulation of
p53 by Mdm2 and
Mdm4 is critical in cardiac endocardial cushion morphogenesis during heart development
Liu et al., Cancer Sci 2012
(Leukemia, Lymphocytic, Chronic, B-Cell) :
FL-MDM4 inhibitory
effects on
p53 can be removed by MDM2-p53 and saved by Nutlin-3
Li et al., Clin Cancer Res 2013
(Neoplasms) :
Given that Mdm2 and
Mdm4 inhibit
p53 activities to promote tumor development, small molecules and peptides were developed to abrogate the inhibition of p53 by Mdm proteins
Xiong et al., Chinese journal of cancer 2013
:
Disrupting the Mdm2 and Mdm4 interaction using knockin mice models causes embryonic lethality that can be completely rescued by the concomitant loss of p53, suggesting that Mdm2 and
Mdm4 heterodimerization is critical to
inhibit p53 activity during embryogenesis ... Studies from these mouse models strongly suggest that blocking Mdm2- and
Mdm4 mediated
p53 inhibition is an appealing therapeutic strategy for cancer patients with wild-type p53 alleles