An essential function of the extreme C-terminus of MDM2 can be provided by MDMX

Pannekoek, W., Uldrijan, S. and Vousden, K. (2007) An essential function of the extreme C-terminus of MDM2 can be provided by MDMX. EMBO Journal, 26(1), pp. 102-112. (doi: 10.1038/sj.emboj.7601469)

Abstract

MDM2 (HDM2) is a ubiquitin ligase that can target the p53 tumor suppressor protein for degradation. The RING domain is essential for the E3 activity of MDM2, and we show here that the extreme C-terminal tail of MDM2 is also critical for efficient E3 activity. Loss of E3 function in MDM2 mutants deleted of the C-terminal tail correlated with a failure of these mutants to oligomerize with MDM2, or with the related protein MDMX (HDMX). However, MDM2 containing point mutations within the C-terminus that inactivated E3 function retained the ability to oligomerize with the wild-type MDM2 RING domain and MDMX, and our results indicate that oligomers containing both wild-type MDM2 and a C-terminal mutant protein retain E3 function both in auto-degradation and degradation of p53. Interestingly, the E3 activity of C-terminal point mutants of MDM2 can also be supported by interaction with wild-type MDMX, suggesting that MDMX can directly contribute to E3 function.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Uldrijan, Mr Stjepan and Vousden, Karen
• Authors: Pannekoek, W., Uldrijan, S., and Vousden, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: EMBO Journal
• ISSN: 0261-4189