Reactome: A Curated Pathway Database

MDM2 ubiquitinates TP53

Stable Identifier
R-HSA-6804879
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
Participants
Participant Of
This entity is regulated by:
Title Physical Entity Activity
ubiquitin protein ligase activity of p-S166,S188-MDM2 dimer, p-S166,S188-MDM2,MDM4:TP53 [nucleoplasm] p-S166,S188-MDM2 dimer, p-S166,S188-MDM2,MDM4:TP53 [nucleoplasm] ubiquitin protein ligase activity (0061630)
Orthologous Events