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1 Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom and
2 Chirurgische Universitätskliniken Ulm, Department of Visceral and Transplantation Surgery, Ulm, Germany
Requests for reprints: David W. Meek, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom. Phone: 44-01382-660111. E-mail: meek{at}cancer.org.uk
Abstract
The functions of the MDM2 protein, in particular its E3 ubiquitin ligase activity and its ability to interact with a number of cellular proteins intimately involved in growth regulation, are modulated by sumoylation and multisite phosphorylation. These posttranslational mechanisms not only regulate the intrinsic activity of MDM2 in response to cellular stresses, but also govern its subcellular localization, differentiate between MDM2-mediated ubiquitination of p53 and autoubiquitination, integrate the stress response with mechanisms that mediate cell survival, and modulate the interaction of MDM2 with cellular and viral proteins. In this review, we summarize our current knowledge of the role of posttranslational modifications of MDM2 and their functional relevance.
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