Biol. Pharm. Bull., 30(2),359-362, February 2007

Notes

Checkpoint Kinase 1 Is Cleaved in a Caspase-Dependent Pathway during Genotoxic Stress-Induced Apoptosis

Naoyuki OKITA,^a Yuki KUDO,^a and Sei-ichi TANUMA^*,a,b

^a Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science; and ^b Genome & Drug Research Center, Tokyo University of Science; 2641 Yamazaki, Noda, Chiba 278-8510, Japan. * To whom correspondence should be addressed. e-mail: tanuma@rs.noda.tus.ac.jp

Checkpoint kinase 1 (Chk1) plays important roles in genotoxic stress-induced cell cycle checkpoint and in normal cell cycle progression. Here, we show that Chk1 is cleaved in the treatment of apoptotic dose of etoposide (ETP) or cisplatin (CIS) but not of viable dose in HeLa S3 cells. The cleavage of Chk1 was completely inhibited by an irreversible and cell-permeable pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-fmk). These results identify Chk1 as a novel substrate that is cleaved by a caspase-dependent manner during genotoxic stress-induced apoptosis. Our data may also indicate the existence of a novel Chk1-regulated apoptotic pathway.

Key words checkpoint kinase 1 (Chk1); genotoxic stress; cell cycle checkpoint; DNA repair; apoptosis; caspase