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

J. Biol. Chem., Vol. 282, Issue 41, 30311-30321, October 12, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/41/30311    most recent M704642200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kass, E. M. Articles by Prives, C. Search for Related Content PubMed PubMed Citation Articles by Kass, E. M. Articles by Prives, C. Social Bookmarking                      What's this?

Stability of Checkpoint Kinase 2 Is Regulated via Phosphorylation at Serine 456^*

Elizabeth M. Kass, Jinwoo Ahn¹, Tomoaki Tanaka², William A. Freed-Pastor, Susan Keezer, and Carol Prives³

From the Department of Biological Sciences, Columbia University, New York, New York, 10027 and Cell Signaling Technology, Inc., Danvers, Massachusetts 01923

Checkpoint kinase 2 (Chk2), a DNA damage-activated protein kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites. Using mass spectrometry we identified a new Chk2 phosphorylation site at Ser-456. We show that phosphorylation of Ser-456 plays a role in the regulation of Chk2 stability particularly after DNA damage. Mutation of Ser-456 to alanine results in hyperubiquitination of Chk2 and dramatically reduced Chk2 stability. Furthermore, cells expressing S456A Chk2 show a reduction in the apoptotic response to DNA damage. These findings suggest a mechanism for stabilization of Chk2 in response to DNA damage via phosphorylation at Ser-456 and proteasome-dependent turnover of Chk2 protein via dephosphorylation of the same residue.

Received for publication, June 6, 2007 , and in revised form, August 21, 2007.

^* This work was supported by NCI, National Institutes of Health (NIH) Grant 87497 and NIH Medical Scientist Training Program Training Grant 5T32 GM07367. 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 Fig. S1.

¹ Present address: Dept. of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15260.

² Present address: Dept. of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

³ To whom correspondence should be addressed: Dept. of Biological Sciences, Columbia University, New York, NY 10027. Tel.: 212-854-2557; Fax: 212-865-8246; E-mail: clp3{at}columbia.edu.

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

This article has been cited by other articles:

				Y.-j. Xu and T. J. Kelly Autoinhibition and Autoactivation of the DNA Replication Checkpoint Kinase Cds1 J. Biol. Chem., June 5, 2009; 284(23): 16016 - 16027. [Abstract] [Full Text] [PDF]

				J. Li, I. A. Taylor, J. Lloyd, J. A. Clapperton, S. Howell, D. MacMillan, and S. J. Smerdon Chk2 Oligomerization Studied by Phosphopeptide Ligation: IMPLICATIONS FOR REGULATION AND PHOSPHODEPENDENT INTERACTIONS J. Biol. Chem., December 19, 2008; 283(51): 36019 - 36030. [Abstract] [Full Text] [PDF]

				C. M. Lovly, L. Yan, C. E. Ryan, S. Takada, and H. Piwnica-Worms Regulation of Chk2 Ubiquitination and Signaling through Autophosphorylation of Serine 379 Mol. Cell. Biol., October 1, 2008; 28(19): 5874 - 5885. [Abstract] [Full Text] [PDF]