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Originally published In Press as doi:10.1074/jbc.M301346200 on July 7, 2003

J. Biol. Chem., Vol. 278, Issue 39, 37745-37752, September 26, 2003
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Plakoglobin Is O-Glycosylated Close to the N-terminal Destruction Box*

Sarah Hatsell {ddagger}, Lillian Medina §, Joe Merola {ddagger}, Robert Haltiwanger § and Pamela Cowin {ddagger} ¶

From the {ddagger}Departments of Cell Biology and Dermatology, New York University Medical School, New York, New York 10016 and the §Department of Biochemistry and Cell Biology, State University of New York (SUNY), Institute for Cell and Developmental Biology, Stony Brook, New York 11794-5215

Plakoglobin provides a key linkage in protein chains that connect desmosomal and classical cadherins to the cytoskeleton. It is also present in a significant cytosolic pool that has the capacity to impact on canonical Wnt signaling by competing for interaction with partner proteins of {beta}-catenin. The closely related protein, {beta}-catenin, is rapidly targeted for proteasomal degradation by phosphorylation of a "destruction box" within the N-terminal domain. Inhibition of this process forms the basis of Wnt signaling. This destruction box is also found in the N-terminal domain of plakoglobin. We report that plakoglobin is modified by the addition of O-GlcNAc at a single site in close proximity to the destruction box. O-GlcNAc modification has been proposed to counteract phosphorylation, provide protection from proteasomal degradation, mediate signal transduction, silence transcription, and regulate multimolecular protein assembly. This finding has potential implications for understanding the roles of plakoglobin.


Received for publication, February 6, 2003 , and in revised form, June 27, 2003.

* This work was supported by National Institutes of Health GM47429 (to P. C.) and a New York State Health Research Science Board fellowship (to S. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 212-263-8715; Fax: 212-263-8139; E-mail: cowinp01{at}med.nyu.edu.


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