Gene interactions and pathways from curated databases and text-mining

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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 *

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