MDM2: a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 via Akt-mediated MDM2 phosphorylation. Phosphorylation of MDM2 increases its interaction with p300, providing a platform to allow the assembly of the protein complex necessary for MDM2-mediated ubiquitination and degradation of p53. Phosphorylation of MDM2 also blocks its binding to p19ARF, increasing the degradation of p53. Facilitates the nuclear export of p53 and targets it for proteasome-mediated proteolysis. Eight alternatively spliced isoforms have been reported.
Protein type: Inhibitor; Ubiquitin ligase; Oncoprotein; Ligase; EC 6.3.2.19; Nucleolus; Ubiquitin conjugating system; EC 6.3.2.-
Chromosomal Location of Human Ortholog: 12q14.3-q15
Cellular Component: nucleoplasm; nuclear body; protein complex; cytoplasm; nucleolus; plasma membrane; synapse; cytosol; nucleus
Molecular Function: identical protein binding; peroxisome proliferator activated receptor binding; protein binding; enzyme binding; zinc ion binding; p53 binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; ligase activity
Biological Process: nerve growth factor receptor signaling pathway; viral reproduction; protein ubiquitination during ubiquitin-dependent protein catabolic process; response to morphine; protein ubiquitination; negative regulation of transcription from RNA polymerase II promoter; negative regulation of caspase activity; positive regulation of mitotic cell cycle; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; response to carbohydrate stimulus; positive regulation of protein export from nucleus; response to antibiotic; negative regulation of DNA damage response, signal transduction by p53 class mediator; synaptic transmission; establishment of protein localization; response to magnesium ion; peptidyl-lysine modification; positive regulation of cell proliferation; protein complex assembly; response to iron ion; response to drug; epidermal growth factor receptor signaling pathway; traversing start control point of mitotic cell cycle; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; protein destabilization; response to cocaine; response to ether; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; innate immune response; regulation of protein catabolic process; negative regulation of transcription, DNA-dependent
Disease: Accelerated Tumor Formation, Susceptibility To
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