RRC ID 18962
著者 Ikai N, Nakazawa N, Hayashi T, Yanagida M.
タイトル The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe.
ジャーナル Open Biol
Abstract Target of rapamycin complexes (TORCs), which are vital for nutrient utilization, contain a catalytic subunit with the phosphatidyl inositol kinase-related kinase (PIKK) motif. TORC1 is required for cell growth, while the functions of TORC2 are less well understood. We show here that the fission yeast Schizosaccharomyces pombe TORC2 has a cell cycle role through determining the proper timing of Cdc2 Tyr15 dephosphorylation and the cell size under limited glucose, whereas TORC1 restrains mitosis and opposes securin-separase, which are essential for chromosome segregation. These results were obtained using the previously isolated TORC1 mutant tor2-L2048S in the phosphatidyl inositol kinase (PIK) domain and a new TORC2 mutant tor1-L2045D, which harbours a mutation in the same site. While mutated TORC1 and TORC2 displayed diminished kinase activity and FKBP12/Fkh1-dependent rapamycin sensitivity, their phenotypes were nearly opposite in mitosis. Premature mitosis and the G2-M delay occurred in TORC1 and TORC2 mutants, respectively. Surprisingly, separase/cut1-securin/cut2 mutants were rescued by TORC1/tor2-L2048S mutation or rapamycin addition or even Fkh1 deletion, whereas these mutants showed synthetic defect with TORC2/tor1-L2045D. TORC1 and TORC2 coordinate growth, mitosis and cell size control, such as Wee1 and Cdc25 do for the entry into mitosis.
巻・号 1(3)
ページ 110007
公開日 2011-11-1
DOI 10.1098/rsob.110007
PII rsob110007
PMID 22645648
PMC PMC3352084
MeSH Amino Acid Sequence Amino Acid Substitution Bridged Bicyclo Compounds, Heterocyclic / pharmacology CDC2 Protein Kinase / metabolism Cell Cycle Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Division Endopeptidases / genetics Endopeptidases / metabolism* Genes, Fungal Mitosis Molecular Sequence Data Mutation Phosphatidylinositol 3-Kinases / chemistry Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Protein Kinases / chemistry Protein Kinases / genetics Protein Kinases / metabolism* Protein Subunits Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Schizosaccharomyces / cytology Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces / growth & development Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Securin Separase Sequence Homology, Amino Acid Sirolimus / pharmacology Spindle Apparatus / drug effects Spindle Apparatus / genetics Thiazolidines / pharmacology
IF 4.931
引用数 42
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
酵母 Dclp1