The Fission Yeast TOR Homolog,tor1 +, Is Required for the Response to Starvation and Other Stresses via a Conserved Serine*

Targets of rapamycin (TORs) are conserved phosphatidylinositol kinase-related kinases that are involved in the coordination between nutritional or mitogenic signals and cell growth. Here we report the initial characterization of twoSchizosaccharomyces pombe TOR homologs,tor1 + and tor2 +.tor2 + is an essential gene, whereastor1 + is required only under starvation and other stress conditions. Specifically, Δtor1 cells fail to enter stationary phase or undergo sexual development and are sensitive to cold, osmotic stress, and oxidative stress. In complex with the prolyl isomerase FKBP12, the drug rapamycin binds a conserved domain in TORs, FRB, thus inhibiting some of the functions of TORs. Mutations at a conserved serine within the FRB domain ofSaccharomyces cerevisiae TOR proteins led to rapamycin resistance but did not otherwise affect the functions of the proteins. The S. pombe tor1 + exhibits different features; substitution of the conserved serine residue, Ser1834, with arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S. pombe.

[1]  S. Schreiber,et al.  Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Michael N. Hall,et al.  The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors , 1999, Nature.

[3]  J. Heitman,et al.  Antifungal Activities of Antineoplastic Agents:Saccharomyces cerevisiae as a Model System To Study Drug Action , 1999, Clinical Microbiology Reviews.

[4]  J. Heitman,et al.  TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals , 1999, Molecular and Cellular Endocrinology.

[5]  S. Forsburg,et al.  The best yeast? , 1999, Trends in genetics : TIG.

[6]  S. Forsburg,et al.  Rereplication phenomenon in fission yeast requires MCM proteins and other S phase genes. , 1999, Genetics.

[7]  J. Heitman,et al.  Rapamycin Antifungal Action Is Mediated via Conserved Complexes with FKBP12 and TOR Kinase Homologs inCryptococcus neoformans , 1999, Molecular and Cellular Biology.

[8]  J. Davey.  Fusion of a fission yeast , 1998, Yeast.

[9]  A. Schmidt,et al.  The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease , 1998, The EMBO journal.

[10]  J. Heitman,et al.  Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway , 1998, Molecular and Cellular Biology.

[11]  Takeshi Noda,et al.  Tor, a Phosphatidylinositol Kinase Homologue, Controls Autophagy in Yeast* , 1998, The Journal of Biological Chemistry.

[12]  M. Kasuga,et al.  Regulation of eIF-4E BP1 Phosphorylation by mTOR* , 1997, The Journal of Biological Chemistry.

[13]  M. Choder,et al.  Rapamycin specifically interferes with the developmental response of fission yeast to starvation , 1997, Journal of bacteriology.

[14]  Christine C. Hudson,et al.  Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. , 1997, Science.

[15]  M Aldea,et al.  A Set of Vectors with a Tetracycline‐Regulatable Promoter System for Modulated Gene Expression in Saccharomyces cerevisiae , 1997, Yeast.

[16]  S. Forsburg,et al.  General purpose tagging vectors for fission yeast. , 1997, Gene.

[17]  S. Schreiber,et al.  Target of rapamycin proteins and their kinase activities are required for meiosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Marc Bickle,et al.  The Yeast Phosphatidylinositol Kinase Homolog TOR2 Activates RHO1 and RHO2 via the Exchange Factor ROM2 , 1997, Cell.

[19]  M. Hall,et al.  TOR2 is required for organization of the actin cytoskeleton in yeast. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Jan E. Schnitzer,et al.  Role of GTP Hydrolysis in Fission of Caveolae Directly from Plasma Membranes , 1996, Science.

[21]  P. Russell,et al.  Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. , 1996, Genes & development.

[22]  T. Toda,et al.  The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. , 1996, Genes & development.

[23]  K. Arndt,et al.  Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. , 1996, Genes & development.

[24]  M. Hall,et al.  The TOR signalling pathway and growth control in yeast. , 1996, Biochemical Society transactions.

[25]  I. Stansfield,et al.  An MBoC Favorite: TOR controls translation initiation and early G1 progression in yeast , 2012, Molecular biology of the cell.

[26]  T. Toda,et al.  Schizosaccharomyces pombe atf1+ encodes a transcription factor required for sexual development and entry into stationary phase. , 1995, The EMBO journal.

[27]  J. Heitman,et al.  TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin (*) , 1995, The Journal of Biological Chemistry.

[28]  S. Schreiber,et al.  Control of p70 S6 kinase by kinase activity of FRAP in vivo , 1995, Nature.

[29]  Stuart L. Schreiber,et al.  TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin , 1995, Cell.

[30]  S. Schreiber,et al.  Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Mclaughlin,et al.  Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue. , 1994, The Journal of biological chemistry.

[32]  V. Berlin,et al.  RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[34]  S. Moreno,et al.  Regulation of progression through the Gl phase of the cell cycle by the rum1 + gene , 1994, Nature.

[35]  J. Kunz,et al.  TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. , 1994, Molecular biology of the cell.

[36]  M. Mclaughlin,et al.  Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity , 1993, Molecular and cellular biology.

[37]  J. Kunz,et al.  Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression , 1993, Cell.

[38]  H. Prentice,et al.  High efficiency transformation of Schizosaccharomyces pombe by electroporation. , 1992, Nucleic acids research.

[39]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.

[40]  S. Ho,et al.  Site-directed mutagenesis by overlap extension using the polymerase chain reaction. , 1989, Gene.

[41]  D. Beach,et al.  Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccharomyces pombe , 1986, Molecular and cellular biology.