Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

18 (22): 6455-6461

Copyright © 1999 by the European Molecular Biology Organization.

The EMBO Journal Vol. 18,pp. 6455-6461, 1999, Copyright © European Molecular Biology Organization

SUMO-1 modification activates the transcriptional response of p53

Manuel S. Rodriguez, Joana M.P. Desterro, Sonia Lain, Carol A. Midgley, David P. Lane and Ronald T. Hay

School of Biomedical Science, BMS Building, University of St Andrews, St Andrews, Fife KY16 9ST and 1 Cancer Research Campaign Laboratories, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, Scotland, UK
2   Corresponding author
   e-mail: rth{at}st-and.ac.uk
   M.S.Rodriguez and J.M.P.Desterro contributed equally to this work

The p53 tumour suppressor protein is regulated by ubiquitin-mediated proteasomal degradation. In normal cells p53 is constitutively ubiquitylated by the Mdm2 ubiquitin ligase. When the p53 response is activated by stress signals p53 levels rise due to inhibition of this degradative pathway. Here we show that p53 is modified by the small ubiquitin-like protein SUMO-1 at a single site, K386, in the C-terminus of the protein. Modification in vitro requires only SUMO-1, the SUMO-1 activating enzyme and ubc9. SUMO-1 and ubiquitin modification do not compete for the same lysine acceptor sites in p53. Overexpression of SUMO-1 activates the transcriptional activity of wild-type p53, but not K386R p53 where the SUMO-1 acceptor site has been mutated. The SUMO-1 modification pathway therefore acts as a potential regulator of the p53 response and may represent a novel target for the development of therapeutically useful modulators of the p53 response.

Keywords: mdm2/p53/SUMO-1/ubiquitin

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882