别名
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E3 ubiquitin-protein ligase Mdm2, 6.3.2.-, Double minute 2 protein, Hdm2, Oncoprotein Mdm2, p53-binding protein Mdm2,
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功能
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E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibit
s p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also ac
ts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent
ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitin
ation and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component
of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination a
nd subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal de
gradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, , PubMed:190
98711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, , PubMed:2212891
1). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule ce
lls (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor end
ocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative str
ess, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic rete
ntion rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I a
nd complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903).
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组织表达
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Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform M
dm2-G are observed in a range of cancers but absent in normal tissues
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细胞定位
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Nucleus, nucleoplasm. Cytoplasm. Nucleus, nucleolus. Nucleus. Note=Expressed predominantly in the nucleoplasm. Interacti
on with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in bo
th ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF
1 isoform A in the nucleus
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