Journal
FEBS LETTERS
Volume 584, Issue 22, Pages 4695-4702Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.10.049
Keywords
MDM2; RING-finger; p53; Motility; Invasion; Ubiquitin-ligase
Funding
- Cancer Research UK
- Mersey Kidney Research
- North West Cancer Research Fund
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Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein-protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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