title: Checkpoint kinase 1 is cleaved in a caspase-dependent pathway during genotoxic stress-induced apoptosis.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Okita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kudo
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D002945:Cisplatin; D053938:DNA Fragmentation; D005047:Etoposide; D006367:HeLa Cells; D006801:Humans; D009153:Mutagens; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D009153:Mutagens; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D005047:Etoposide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D020169:Caspases; D002945:Cisplatin