p53 negative regulator Mdm2/Mdm4 (IPR016495)

Short name: p53_neg-reg_MDM_2/4

Overlapping homologous superfamilies


Family relationships


This group represents a p53 negative regulator Mdm2/Mdm4.

MDM2 is an oncoprotein that acts as a cellular inhibitor of the p53 tumour suppressor by binding to the transactivation domain of p53 and suppressing its ability to activate transcription [PMID: 8875929]. In addition, MDM2 acts as an E3 ubiquitin ligase responsible for the ubiquitination and subsequent degradation of p53 [PMID: 14707282]. P53 acts in response to DNA damage, inducing cell cycle arrest and apoptosis. Inactivation of p53 is a common occurrence in neoplastic transformations. MDM2 is also known to have p53-independent functions.

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.

MDM4, also known as MDMX, is a MDM2-related protein that has also been shown to inhibit p53, although not as well as MDM2. Most studies have not been able to ascribe E3 ligase function to MDM4.

GO terms

Biological Process

GO:0043066 negative regulation of apoptotic process
GO:0071157 negative regulation of cell cycle arrest

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0005634 nucleus

Contributing signatures

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