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Mol. Cell. Biol. 32 (14): 2709-2721

Copyright © 2012 by the American Society for Microbiology. All rights reserved.

Identification of Estrogen Receptor β as a SUMO-1 Target Reveals a Novel Phosphorylated Sumoylation Motif and Regulation by Glycogen Synthase Kinase 3β

Nathalie Picard,a,b Véronique Caron,a Stéphanie Bilodeau,a,b Mélanie Sanchez,a,b Xavier Mascle,b Muriel Aubry,b, and André Tremblaya,b,c

Sainte-Justine Hospital Research Center,a Departments of Biochemistry,b Obstetrics and Gynecology, University of Montreal, Montréal, Québec, Canadac,c

Received for publication 25 November 2011. Revision received 27 December 2011. Accepted for publication 30 April 2012.

Abstract: SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor β (ERβ) to be a new target of SUMO-1. ERβ SUMO-1 modification occurs on a unique nonconsensus sumoylation motif which becomes fully competent upon phosphorylation of its contained serine residue, which provides the essential negative charge for sumoylation. This process is further regulated by phosphorylation of additional adjacent serine residues by glycogen synthase kinase 3β (GSK3β), which maximizes ERβ sumoylation in response to hormone. SUMO-1 attachment prevents ERβ degradation by competing with ubiquitin at the same acceptor site and dictates ERβ transcriptional inhibition by altering estrogen-responsive target promoter occupancy and gene expression in breast cancer cells. These findings uncovered a novel phosphorylated sumoylation motif (pSuM), which consists of the sequence {psi}KXS (where {psi} represents a large hydrophobic residue) and which is connected to a GSK3-activated extension that functions as a SUMO enhancer. This extended pSuM offers a valuable signature to predict SUMO substrates under protein kinase regulation.


Address correspondence to André Tremblay, andre.tremblay.1{at}umontreal.ca.

Published ahead of print 14 May 2012

Supplemental material for this article may be found at http://mcb.asm.org/.



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