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: Ubiquitin ligase; Ubiquitin conjugating system; EC 6.3.2.19; Nucleolus; EC 6.3.2.-; Oncoprotein; Ligase; Inhibitor
Chromosomal Location of Human Ortholog: 12q14.3-q15
Cellular Component: cytoplasm; cytosol; nuclear body; nucleolus; nucleoplasm; nucleus; plasma membrane; protein complex; synapse
Molecular Function: enzyme binding; identical protein binding; ligase activity; p53 binding; peroxisome proliferator activated receptor binding; protein binding; SUMO ligase activity; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; zinc ion binding
Biological Process: blood vessel development; blood vessel remodeling; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; establishment of protein localization; negative regulation of caspase activity; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; peptidyl-lysine modification; positive regulation of cell proliferation; positive regulation of mitotic cell cycle; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein export from nucleus; protein complex assembly; protein destabilization; protein sumoylation; protein ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process; regulation of heart rate; regulation of protein catabolic process; response to antibiotic; response to carbohydrate stimulus; response to cocaine; response to drug; response to ether; response to iron ion; response to magnesium ion; response to morphine; traversing start control point of mitotic cell cycle; viral reproduction
Disease: Accelerated Tumor Formation, Susceptibility To
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