title: S. pombe TORC1 activates the ubiquitin-proteasomal degradation of the meiotic regulator Mei2 in cooperation with Pat1 kinase.
abstract: Target of rapamycin (TOR) kinase regulates cell metabolism and growth, acting as a subunit of two multi-protein complexes, TORC1 and TORC2. Known TORC substrates are either kinases or general factors involved in growth control. Here, we show that fission yeast TORC1, which promotes vegetative growth and suppresses sexual development, can phosphorylate Mei2 (a specific factor involved in switching the cell fate) in vitro. Alanine substitutions at the nine Mei2 phosphorylation sites stabilize the protein and promote mating and meiosis in vivo. We found that Mei2 is polyubiquitylated in vivo in a TORC1-dependent manner. Based on these data, we propose that TORC1 contributes to the suppression of sexual development by phosphorylating Mei2, in addition to controlling the cellular metabolic status.
authors.affiliation: Laboratory of Gene Function, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Otsubo
authors.affiliation: Laboratory of Gene Function, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan.
authors.forename: Hayao
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Laboratory of Gene Function, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan Laboratory of Cell Responses, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi, 444-8585, Japan yamamoto@nibb.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D004843:Epistasis, Genetic; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D058570:TOR Serine-Threonine Kinases; C088896:mei2 protein, S pombe; C087019:ran1 protein, S pombe; C513100:tor2 protein, S pombe
keywords: Fission yeast; Mating; Mei2; Meiosis; Proteasome; TOR kinase