title: Activation of apoptosis by caspase-3-dependent specific RelB cleavage in anticancer agent-treated cancer cells: involvement of positive feedback mechanism.
abstract: DTCM-glutarimide (DTCM-G) is a newly found anti-inflammatory agent. In the course of experiments with lymphoma cells, we found that DTCM-G induced specific RelB cleavage. Anticancer agent vinblastine also induced the specific RelB cleavage in human fibrosarcoma HT1080 cells. The site-directed mutagenesis analysis revealed that the Asp205 site in RelB was specifically cleaved possibly by caspase-3 in vinblastine-treated HT1080 cells. Moreover, the cells stably overexpressing RelB Asp205Ala were resistant to vinblastine-induced apoptosis. Thus, the specific Asp205 cleavage of RelB by caspase-3 would be involved in the apoptosis induction by anticancer agents, which would provide the positive feedback mechanism.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Kuboki
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Siro
authors.initials: S
authors.lastname: Simizu
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195, Japan. Electronic address: umezawa@aichi-med-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001224:Aspartic Acid / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism*; D025461:Feedback, Physiological; D006801:Humans; D010881:Piperidones / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D059748:Proteolysis / Q000187:drug effects; D051841:Transcription Factor RelB / Q000737:chemistry / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: C573776:3-((dodecylthiocarbonyl)methyl)glutarimide; D000970:Antineoplastic Agents; D010881:Piperidones; C497593:RELB protein, human; D051841:Transcription Factor RelB; D001224:Aspartic Acid; D014747:Vinblastine; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Caspase-3; DTCM-glutarimide; RelB; Vinblastine