E3 ubiquitin-protein ligase Mdm2 (IPR028340)

Short name: Mdm2

Overlapping homologous superfamilies

Family relationships


MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome [PMID: 14707283]. p53 acts as an important defense mechanism against cancer, and is negatively regulated by interaction with the oncoprotein MDM2 [PMID: 14707283]. MDM2 overexpression correlates with metastasis and advanced forms of several cancers and may be used as a cancer drug target [PMID: 23885265]. In addition, MDM2 has important roles in the cell independent of p53. It interacts with several proteins such as Rb/E2F-1 complex [PMID: 18541670], the DNA methyltransferase DNMT3A [PMID: 22733537], p107 [PMID: 8570197], MTBP [PMID: 15632057] and the cyclin kinase inhibitor p21 [PMID: 20308078]. MDM2 also affects cell apoptosis [PMID: 19321440, PMID: 19411066].

The core of MDM2 folds into an open bundle of four helices which is capped by two small 3-stranded beta-sheets. It consists of a duplication of two structural repeats. MDM2 has a deep hydrophobic cleft on which the p53 alpha-helix binds; p53 residues involved in transactivation are buried deep within the cleft of MDM2, thereby concealing the p53 transactivation domain. In addition to its N-terminal p53 binding domain, MDM2 contains a central acidic domain, zinc finger domain and a C-terminal RING-finger domain.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.