HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 6, 3614-3624, February 10, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/6/3614    most recent M508258200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dusek, R. L. Articles by Green, K. J. Search for Related Content PubMed PubMed Citation Articles by Dusek, R. L. Articles by Green, K. J. Social Bookmarking                      What's this?

The Differentiation-dependent Desmosomal Cadherin Desmoglein 1 Is a Novel Caspase-3 Target That Regulates Apoptosis in Keratinocytes^*

Rachel L. Dusek¹, Spiro Getsios², Feng Chen, Jung K. Park, Evangeline V. Amargo, Vincent L. Cryns, and Kathleen J. Green³

From the Departments of Pathology and Dermatology and Cell Death Regulation Laboratory, Departments of Medicine and Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611

Although a number of cell adhesion proteins have been identified as caspase substrates, the potential role of differentiation-specific desmosomal cadherins during apoptosis has not been examined. Here, we demonstrate that UV-induced caspase cleavage of the human desmoglein 1 cytoplasmic tail results in distinct 17- and 140- kDa products, whereas metalloproteinase-dependent shedding of the extracellular adhesion domain generates a 75-kDa product. In vitro studies identify caspase-3 as the preferred enzyme that cleaves desmoglein 1 within its unique repeating unit domain at aspartic acid 888, part of a consensus sequence not conserved among the other desmosomal cadherins. Apoptotic processing leads to decreased cell surface expression of desmoglein 1 and re-localization of its C terminus diffusely throughout the cytoplasm over a time course comparable with the processing of other desmosomal proteins and cytoplasmic keratins. Importantly, whereas classic cadherins have been reported to promote cell survival, short hairpin RNA-mediated suppression of desmoglein 1 in differentiated keratinocytes protected cells from UV-induced apoptosis. Collectively, our results identify desmoglein 1 as a novel caspase and metalloproteinase substrate whose cleavage likely contributes to the dismantling of desmosomes during keratinocyte apoptosis and also reveal desmoglein 1 as a previously unrecognized regulator of apoptosis in keratinocytes.

Received for publication, July 28, 2005 , and in revised form, October 25, 2005.

^* This work was supported in part by National Institutes of Health Grant R01AR41836 with partial support from National Institutes of Health Grant P01 DE12328. 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.

¹ Supported in part by National Institutes of Health Predoctoral Training Grant T32 CA09560.

² Supported by a postdoctoral fellowship from the Canadian Institutes of Health Research.

³ To whom correspondence should be addressed: Depts. of Pathology and Dermatology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: 312-503-5300; Fax: 312-503-8240; E-mail: kgreen{at}northwestern.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Nava, M. G. Laukoetter, A. M. Hopkins, O. Laur, K. Gerner-Smidt, K. J. Green, C. A. Parkos, and A. Nusrat Desmoglein-2: A Novel Regulator of Apoptosis in the Intestinal Epithelium Mol. Biol. Cell, November 1, 2007; 18(11): 4565 - 4578. [Abstract] [Full Text] [PDF]

				M. E. Werner, F. Chen, J. V. Moyano, F. Yehiely, J. C. R. Jones, and V. L. Cryns Caspase Proteolysis of the Integrin beta4 Subunit Disrupts Hemidesmosome Assembly, Promotes Apoptosis, and Inhibits Cell Migration J. Biol. Chem., February 23, 2007; 282(8): 5560 - 5569. [Abstract] [Full Text] [PDF]