MDM2 ubiquitinates TP53

Stable Identifier
R-HSA-6804879
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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MDM2 is an ubiquitin ligase whose expression is positively regulated by TP53 (p53) (Wu et al. 1993). MDM2 binds TP53 tetramer (Maki 1999) and promotes its ubiquitination and subsequent degradation (Fuchs et al. 1998). Formation of MDM2 homodimers (Cheng et al. 2011) or heterodimers with MDM4 (MDMX) is needed for efficient ubiquitination of TP53 (Linares et al. 2003). While MDM2-TP53 binding occurs at the amino-terminus of TP53, MDM2 ubiquitinates TP53 lysine residues at the carboxy-terminus. Acetylation of those lysines can inhibit MDM2-dependent ubiquitination (Li et al. 2002).

Literature References
PubMed ID Title Journal Year
8319905 The p53-mdm-2 autoregulatory feedback loop

Wu, X, Bayle, JH, Olson, D, Levine, AJ

Genes Dev. 1993
12421820 Acetylation of p53 inhibits its ubiquitination by Mdm2

Li, M, Luo, J, Brooks, CL, Gu, W

J. Biol. Chem. 2002
21986495 Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage

Cheng, Q, Cross, B, Li, B, Chen, L, Li, Z, Chen, J

Mol. Cell. Biol. 2011
9824166 Mdm2 association with p53 targets its ubiquitination

Fuchs, SY, Adler, V, Buschmann, T, Wu, X, Ronai, Z

Oncogene 1998
10722742 Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53

Fang, S, Jensen, JP, Ludwig, RL, Vousden, KH, Weissman, AM

J. Biol. Chem. 2000
14507994 HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53

Linares, LK, Hengstermann, A, Ciechanover, A, Muller, S, Scheffner, M

Proc. Natl. Acad. Sci. U.S.A. 2003
10347217 Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2

Maki, CG

J. Biol. Chem. 1999
Participants
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Catalyst Activity
Catalyst Activity
Title
ubiquitin protein ligase activity of p-S166,S188-MDM2 dimer, p-S166,S188-MDM2,MDM4:TP53 [nucleoplasm]
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This event is regulated
Orthologous Events
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