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: Ligase; Ubiquitin conjugating system; Ubiquitin ligase; Inhibitor; Oncoprotein; EC 6.3.2.19; Nucleolus; EC 6.3.2.-
Cellular Component: nucleoplasm; nuclear body; protein complex; cytoplasm; plasma membrane; nucleolus; synapse; cytosol; nucleus
Molecular Function: identical protein binding; peroxisome proliferator activated receptor binding; zinc ion binding; p53 binding; coenzyme F420-2 alpha-glutamyl ligase activity; metal ion binding; ubiquitin-protein ligase activity; ribosomal S6-glutamic acid ligase activity; protein binding; enzyme binding; UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase activity; ubiquitin protein ligase binding; coenzyme F420-0 gamma-glutamyl ligase activity; ligase activity
Biological Process: traversing start control point of mitotic cell cycle; protein destabilization; protein ubiquitination during ubiquitin-dependent protein catabolic process; positive regulation of cell cycle; protein ubiquitination; negative regulation of caspase activity; negative regulation of transcription from RNA polymerase II promoter; positive regulation of mitotic cell cycle; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; positive regulation of protein export from nucleus; negative regulation of DNA damage response, signal transduction by p53 class mediator; establishment of protein localization; peptidyl-lysine modification; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein complex assembly; protein catabolic process; regulation of protein catabolic process; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis
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