| Primary Identifier | IPR016495 | Type | Family |
| Short Name | p53_neg-reg_MDM_2/4 |
| description | 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 []. In addition, MDM2 acts as an E3 ubiquitin ligase responsible for the ubiquitination and subsequent degradation of p53 []. 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 β-sheets. It consists of a duplication of two structural repeats. MDM2 has a deep hydrophobic cleft on which the p53 α-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. |
