Article
- The EMBO Journal (2007) 26, 102 - 112
- doi:10.1038/sj.emboj.7601469
Published online: 14 December 2006
Subject Category:
An essential function of the extreme C-terminus of MDM2 can be provided by MDMX
Stjepan Uldrijan1, Willem-Jan Pannekoek1,a and Karen H Vousden1
- The Beatson Institute for Cancer Research, Glasgow, UK
Correspondence to:
Karen H Vousden, The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. Tel.: +44 141 330 2424; Fax: +44 141 943 0372; E-mail: k.vousden@beatson.gla.ac.uk
aPresent address: Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center, Utrecht, The Netherlands
Received 23 May 2006; Accepted 26 October 2006
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.
Keywords:
- E3,
- MDM2,
- MDMX,
- p53,
- ubiquitin
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
NEWS AND VIEWS
With the ends in sight: images from the BRCA1 tumor suppressor
Nature Structural Biology News and Views (01 Oct 2001)
Balancing Mdm2 ? a Daxx?HAUSP matter
Nature Cell Biology News and Views (01 Aug 2006)
RESEARCH
Actions of Thrombin and Other Coagulant and Proteolytic Enzymes on Blood Platelets
Nature Article (02 Dec 1967)
Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3B
Oncogene Original Article
