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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach

MDM2 bound to MDM4 inhibits TP53. 5 / 5
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"It has been indicated that MDM2 forms a heterodimer or heterooligomer with MDMX through their C-terminal domains to inhibit p53 during early embryogenesis."
"This interaction between MDM2 and MDM4 activates the E3 ligase activity of MDM2 and induces proteosomal degradation of p53 to suppress its endogenous cellular levels below the threshold required for transactivation of target genes, such as the cyclin dependent kinase (CDK) inhibitor p21."
"Although MDM4 alone is unable to target p53 for ubiquitin-proteasome-dependent degradation 6, the MDM2 and MDM4 heterodimer has been shown more potent degrading the p53 protein as compared to the MDM2 homodimer 7, 8."
"Additionally, mutation or deletion of the Mdmx RING also prevents Mdm2 and Mdmx interaction and triggers p53 dependent lethality in vivo."
"In addition, the interaction between p53 and Mdm2 or MdmX suppresses the transcriptional activities of p53."