title: Contribution of caspase(s) to the cell cycle regulation at mitotic phase.
abstract: Caspases have been suggested to contribute to not only apoptosis regulation but also non-apoptotic cellular phenomena. Recently, we have reported the involvement of caspase-7 to the cell cycle progression at mitotic phase by knockdown of caspase-7 using small interfering RNAs and short hairpin RNA. Here we showed that chemically synthesized broad-spectrum caspase inhibitors, which have been used to suppress apoptosis, prevented the cell proliferation in a dose-dependent manner, and that the subtype-specific peptide-based caspase inhibitor for caspase-3 and -7, but not for caspase-9, inhibited cell proliferation. It was also indicated that the BIR2 domain of X-linked inhibitor of apoptosis protein, functioning as an inhibitor for caspase-3 and -7, but not the BIR3 domain which plays as a caspase-9 inhibitor, induced cell cycle arrest. Furthermore, flow cytometry revealed that the cells treated with caspase inhibitors arrested at G(2)/M phase. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, the prevention of the cell proliferation by caspase inhibitors induced cell cycle arrest at mitotic phase accompanying the accumulation of the substrates for APC/C, suggesting the impairment of the APC/C activity at the transition from M to G(1) phases. These results indicate that caspase(s) contribute to the cell cycle regulation at mitotic phase.
authors.affiliation: Biosignal Research Center, Kobe University, Nada-ku, Kobe, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamada
mesh_terms: D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity / Q000187:drug effects; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D010455:Peptides; D011480:Protease Inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D020169:Caspases