title: Chemical genomics approach to identify genes associated with sensitivity to rapamycin in the fission yeast Schizosaccharomyces pombe.
abstract: Rapamycin and its derivatives have now emerged as an attractive therapeutic strategy with both immunosuppressant and antitumor properties. In addition, rapamycin has been proposed as a calorie restriction mimetic to extend the life span of various organisms. The fission yeast Schizosaccharomyces pombe (S. pombe) serves as a valuable genetic model system to study the mechanism(s) of drug action as well as to determine genetic contexts associated with drug sensitivity or resistance. Here, we identified genes that when deleted modulate the rapamycin-sensitive strains in S. pombe. We carried out a chemical genomics screen for rapamycin-sensitive mutants using the genome-deletion library which covers 95.3% of all nonessential fission yeast genes and confirmed 59 genes to be rapamycin sensitive. Gene Ontology (GO) enrichment analysis showed that strains sensitive to rapamycin are highly enriched in processes regulating tRNA modification and mitochondria as well as other ontologies, including cellular metabolic process, chromatin organization, cell cycle, signaling, translation, transport and other cellular processes. Analysis also showed that components of the Elongator complex are overrepresented in the sensitive strains. Here, the data obtained will provide valuable information for speculation on the actions of rapamycin as well as on TORC signaling, thereby presenting a strategy to enhance sensitivity to rapamycin.
authors: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka, 577-8502, Japan; Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo, 102-8472, Japan.
authors: Akira
authors: A
authors: Doi
authors: Ayumi
authors: A
authors: Fujimoto
authors: Shun
authors: S
authors: Sato
authors: Takaya
authors: T
authors: Uno
authors: Yuki
authors: Y
authors: Kanda
authors: Keita
authors: K
authors: Asami
authors: Yuriko
authors: Y
authors: Tanaka
authors: Ayako
authors: A
authors: Kita
authors: Ryosuke
authors: R
authors: Satoh
authors: Reiko
authors: R
authors: Sugiura
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D002453:Cell Cycle; D002843:Chromatin / Q000235:genetics; D025141:Drug Resistance, Fungal; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D008928:Mitochondria / Q000235:genetics; D009154:Mutation; D009287:Naphthyridines / Q000378:metabolism; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C553294:1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one; D000935:Antifungal Agents; D002843:Chromatin; D009287:Naphthyridines; D047428:Protein Kinase Inhibitors; D012343:RNA, Transfer; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus