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

J. Biol. Chem., Vol. 283, Issue 23, 16248-16258, June 6, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/23/16248    most recent M709724200v1 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 Google Scholar Articles by Nogueira, E. Articles by Pombo, C. M. PubMed PubMed Citation Articles by Nogueira, E. Articles by Pombo, C. M. Social Bookmarking                      What's this?

SOK1 Translocates from the Golgi to the Nucleus upon Chemical Anoxia and Induces Apoptotic Cell Death^*

Emilio Nogueira¹², Miguel Fidalgo¹³, Arpad Molnar⁴, John Kyriakis^¶, Thomas Force^||, Juan Zalvide, and Celia M. Pombo⁵

From the Department of Physiology, School of Medicine, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain, Diabetes Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, ^¶Molecular Cardiology Research Institute, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, and ^||Center for Translational Medicine, Thomas Jefferson University, Philadelphia Pennsylvania 19107

SOK1 is a Ste20 protein kinase of the germinal center kinase (GCK) family that has been shown to be activated by oxidant stress and chemical anoxia, a cell culture model of ischemia. More recently, it has been shown to be localized to the Golgi apparatus, where it functions in a signaling pathway required for cell migration and polarization. Herein, we demonstrate that SOK1 regulates cell death after chemical anoxia, as its down-regulation by RNA interference enhances cell survival. Furthermore, expression of SOK1 elicits apoptotic cell death by activating the intrinsic pathway. We also find that a cleaved form of SOK1 translocates from the Golgi to the nucleus after chemical anoxia and that this translocation is dependent on both caspase activity and on amino acids 275-292, located immediately C-terminal to the SOK1 kinase domain. Furthermore, SOK1 entry into the nucleus is important for the cell death response since SOK1 mutants unable to enter the nucleus do not induce cell death. In summary, SOK1 is necessary to induce cell death and can induce death when overexpressed. Furthermore, SOK1 appears to play distinctly different roles in stressed versus non-stressed cells, regulating cell death in the former.

Received for publication, November 28, 2007 , and in revised form, March 24, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant HL67371 (to T. F.) from the NHLBI. This work was also supported by Ministerio de Educación y Ciencia of Spain Grant BMC2002-03110 (to C. P.) and Xunta de Galicia Grants PGIDIT03PXIC20808PN (to C. P.) and PGIDT06PXIB208061PR (to J. Z.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S5.

¹ The first two authors contributed equally to this work.

² A predoctoral fellow from Xunta de Galicia.

³ A predoctoral fellow from Ministerio de Educación y Ciencia of Spain.

⁴ Present address: Medicatus USA, Inc., P. O. Box 290657, Boston, MA 02129.

⁵ To whom correspondence should be addressed: Dept. of Physiology, Laboratory of Cell Signaling and Cancer Research, School of Medicine, University of Santiago de Compostela, San Francisco s/n, 15705 Santiago de Compostela, A Coruña, Spain. Tel.: 34-981-582-658; Fax: 34-981-574-145; E-mail: fspombo{at}usc.es.

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