The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe.
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.
Okinawa Institute of Science and Technology Promotion Corporation, 1919-1 Tancha, Onna, Okinawa 904-0412, Japan.
Nobuyasu
N
Ikai
Norihiko
N
Nakazawa
Takeshi
T
Hayashi
Mitsuhiro
M
Yanagida
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D064247:Separase; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus / Q000494:pharmacology; D008941:Spindle Apparatus / Q000187:drug effects / Q000235:genetics; D053778:Thiazolidines / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D010450:Endopeptidases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D021122:Protein Subunits; D017027:Protein Tyrosine Phosphatases; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D064247:Separase; D020123:Sirolimus; D053778:Thiazolidines; C103135:Cut1 protein, S pombe; C103136:Cut2 protein, S pombe; C523461:Tor1 protein, S pombe; C513100:tor2 protein, S pombe; C469447:cdc2 protein, S pombe; C439269:Clp1 protein, S. pombe; C037067:latrunculin A