title: Identification of genes affecting the toxicity of anti-cancer drug bortezomib by genome-wide screening in S. pombe.
abstract: Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive. We aimed to identify genes affecting the cytotoxicity of Bortezomib in the fission yeast S. pombe as the drug inhibits this organism's cell division cycle like proteasome mutants. Among the 2815 genes screened (covering 56% of total ORFs), 19 genes, whose deletions induce strong synthetic lethality with Bortezomib, were identified. The products of the 19 genes included four ubiquitin enzymes and one nuclear proteasome factor, and 13 of them are conserved in humans. Our results will provide useful information for understanding the actions of Bortezomib within cells.
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology, Okinawa, Japan. takeda@oist.jp
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Ayaka
authors.initials: A
authors.lastname: Mori
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001897:Boronic Acids / Q000633:toxicity*; D000069286:Bortezomib; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics*; D005820:Genetic Testing; D008677:Metaphase / Q000187:drug effects / Q000235:genetics; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011719:Pyrazines / Q000633:toxicity*; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex