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

J. Biol. Chem., Vol. 278, Issue 38, 36163-36168, September 19, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/38/36163    most recent M303795200v1 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 Wu, X. Articles by Chen, J. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by Chen, J. Social Bookmarking                      What's this?

Autophosphorylation of Checkpoint Kinase 2 at Serine 516 Is Required for Radiation-induced Apoptosis^*

Xianglin Wu and Junjie Chen 

From the Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905

In response to ionizing radiation, checkpoint kinase 2 (Chk2) is activated in an ataxia telangiectasia mutation-dependent manner and induces either cell cycle arrest or apoptosis. Chk2 is also autophosphorylated following DNA damage. It is proposed that autophosphorylation of Chk2 may contribute to Chk2 activation. To fully understand the regulation of Chk2, we mapped an in vitro Chk2 autophosphorylation site at C-terminal serine 516 site (Ser-516). Ser-516 of Chk2 is phosphorylated following radiation in vivo, and this phosphorylation depends on the kinase activity of Chk2. Mutation of this autophosphorylation site (S516A) results in reduced Chk2 kinase activity, suggesting that Chk2 autophosphorylation is required for full kinase activation following DNA damage. Moreover, the S516A mutant of Chk2 is defective in ionizing radiation-induced apoptosis, suggesting that Chk2 autophosphorylation is critical for Chk2 function following DNA damage.

Received for publication, April 11, 2003 , and in revised form, June 9, 2003.

^* This work is supported in part by Grant NIH RO1 CA92312 from the National Institutes of Health and grants from Mayo Prostate Specialized Program of Research Excellence, the Prospect Creek Foundation, and the Breast Cancer Research Foundation. 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.

Recipient of Department of Defense Breast Cancer Career Development Award DAMD17-02-1-0472. To whom correspondence should be addressed. Tel.: 507-538-1545; Fax: 507-284-3906; E-mail: chen.junjie{at}mayo.edu.

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

This article has been cited by other articles:

				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]

				E. M. Kass, J. Ahn, T. Tanaka, W. A. Freed-Pastor, S. Keezer, and C. Prives Stability of Checkpoint Kinase 2 Is Regulated via Phosphorylation at Serine 456 J. Biol. Chem., October 12, 2007; 282(41): 30311 - 30321. [Abstract] [Full Text] [PDF]

				A. G. Jobson, J. H. Cardellina II, D. Scudiero, S. Kondapaka, H. Zhang, H. Kim, R. Shoemaker, and Y. Pommier Identification of a Bis-guanylhydrazone [4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a Novel Chemotype for Inhibition of Chk2 Kinase Mol. Pharmacol., October 1, 2007; 72(4): 876 - 884. [Abstract] [Full Text] [PDF]

				A. Yoda, X. Z. Xu, N. Onishi, K. Toyoshima, H. Fujimoto, N. Kato, I. Oishi, T. Kondo, and Y. Minami Intrinsic Kinase Activity and SQ/TQ Domain of Chk2 Kinase as Well as N-terminal Domain of Wip1 Phosphatase Are Required for Regulation of Chk2 by Wip1 J. Biol. Chem., August 25, 2006; 281(34): 24847 - 24862. [Abstract] [Full Text] [PDF]

				S. Leonce, L. Kraus-Berthier, R. M. Golsteyn, M.-H. David-Cordonnier, C. Tardy, A. Lansiaux, V. Poindessous, A. K. Larsen, and A. Pierre Generation of replication-dependent double-strand breaks by the novel n2-g-alkylator s23906-1. Cancer Res., July 15, 2006; 66(14): 7203 - 7210. [Abstract] [Full Text] [PDF]

				R. A. Greenberg, B. Sobhian, S. Pathania, S. B. Cantor, Y. Nakatani, and D. M. Livingston Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes Genes & Dev., January 1, 2006; 20(1): 34 - 46. [Abstract] [Full Text] [PDF]

				S. L. Gibson, R. S. Bindra, and P. M. Glazer Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated-Dependent Manner Cancer Res., December 1, 2005; 65(23): 10734 - 10741. [Abstract] [Full Text] [PDF]

				A. Herman-Antosiewicz and S. V. Singh Checkpoint Kinase 1 Regulates Diallyl Trisulfide-induced Mitotic Arrest in Human Prostate Cancer Cells J. Biol. Chem., August 5, 2005; 280(31): 28519 - 28528. [Abstract] [Full Text] [PDF]

				P. A. Townsend, M. S. Cragg, S. M. Davidson, J. McCormick, S. Barry, K. M. Lawrence, R. A. Knight, M. Hubank, P.-L. Chen, D. S. Latchman, et al. STAT-1 facilitates the ATM activated checkpoint pathway following DNA damage J. Cell Sci., April 15, 2005; 118(8): 1629 - 1639. [Abstract] [Full Text] [PDF]

				M.-B. Yin, Z.-R. Li, S. Cao, F. A. Durrani, R. G. Azrak, C. Frank, and Y. M. Rustum Enhanced 7-Ethyl-10-hydroxycamptothecin (SN-38) Lethality by Methylselenocysteine Is Associated with Chk2 Phosphorylation at Threonine-68 and Down-Regulation of Cdc6 Expression Mol. Pharmacol., July 1, 2004; 66(1): 153 - 160. [Abstract] [Full Text] [PDF]

				H. A. Rogoff, M. T. Pickering, F. M. Frame, M. E. Debatis, Y. Sanchez, S. Jones, and T. F. Kowalik Apoptosis Associated with Deregulated E2F Activity Is Dependent on E2F1 and Atm/Nbs1/Chk2 Mol. Cell. Biol., April 1, 2004; 24(7): 2968 - 2977. [Abstract] [Full Text] [PDF]