QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 26 September 2006
doi: 10.1242/jcs.03200

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.03200v1 119/20/4269    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS 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 Schmitt, E. Articles by Dozier, C. Search for Related Content PubMed PubMed Citation Articles by Schmitt, E. Articles by Dozier, C.

CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage

¹ LBCMCP-CNRS UMR5088, IFR109, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France
² IPBS-CNRS UMR5089, Université Paul Sabatier, 205 route de Narbonne, 31077 Toulouse, France

^* Author for correspondence (e-mail: ducommun{at}cict.fr)

Accepted 4 August 2006

CDC25B is one of the three human phosphatases that activate the CDK-cyclin complexes, thereby triggering cell-cycle progression and division. Commitment to early mitotic events depends on the activation of a centrosomal pool of CDK1–cyclin-B1, and CDC25B is thought to be involved in initiating this centrosomal CDK1–cyclin-B1 activity. Centrosome-associated checkpoint kinase 1 (CHK1) has been proposed to contribute to the proper timing of a normal cell division cycle by inhibiting the activation of the centrosomal pool of CDK1. Here, we show that CDC25B is phosphorylated by CHK1 in vitro on multiple residues, including S230 and S563. We demonstrate these phosphorylations occur in vivo and that they are dependent on CHK1 activity. S230 CHK1-mediated phosphorylation is detected in cell extracts during S phase and G2 phase in the absence of DNA damage. We show that the S230-phosphorylated form of CDC25B is located at the centrosome from early S phase until mitosis. Furthermore, mutation of S230 to alanine increases the mitotic-inducing activity of CDC25B. Our results support a model in which, under normal cell cycle conditions and in the absence of DNA damage, CHK1 constitutively phosphorylates CDC25B during interphase and thus prevents the premature initiation of mitosis by negatively regulating the activity of CDC25B at the centrosome.

Key words: CDC25B, CHK1, Checkpoint kinase, Phosphatase, Cell cycle

Related articles in JCS:

Checkpoint kinase checks out Cdc25B

JCS 2006 119: 2003. [Full Text]  

This article has been cited by other articles:

				R. Boutros, V. Lobjois, and B. Ducommun CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation Cancer Res., December 15, 2007; 67(24): 11557 - 11564. [Abstract] [Full Text] [PDF]

				M. Zhu and R. S. Weiss Increased Common Fragile Site Expression, Cell Proliferation Defects, and Apoptosis following Conditional Inactivation of Mouse Hus1 in Primary Cultured Cells Mol. Biol. Cell, March 1, 2007; 18(3): 1044 - 1055. [Abstract] [Full Text] [PDF]