The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine

被引:158
作者
Weisman, R [1 ]
Choder, M [1 ]
机构
[1] Tel Aviv Univ, Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel
关键词
D O I
10.1074/jbc.M010446200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 two Schizosaccharomyces pombe TOR homologs, tor1(+) and tor2(+). tor2(+) is an essential gene, whereas tor1(+) is required only under starvation and other stress conditions. Specifically, Delta tor1 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 of Saccharomyces 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, Ser(1834), With arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S, pombe.
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页码:7027 / 7032
页数:6
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共 44 条
[1]   TOR controls translation initiation and early G1 progression in yeast [J].
Barbet, NC ;
Schneider, U ;
Helliwell, SB ;
Stansfield, I ;
Tuite, MF ;
Hall, MN .
MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (01) :25-42
[2]   The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors [J].
Beck, T ;
Hall, MN .
NATURE, 1999, 402 (6762) :689-692
[3]   SITE-SPECIFIC MUTAGENESIS OF CDC2+, A CELL-CYCLE CONTROL GENE OF THE FISSION YEAST SCHIZOSACCHAROMYCES-POMBE [J].
BOOHER, R ;
BEACH, D .
MOLECULAR AND CELLULAR BIOLOGY, 1986, 6 (10) :3523-3530
[4]   A MAMMALIAN PROTEIN TARGETED BY G1-ARRESTING RAPAMYCIN-RECEPTOR COMPLEX [J].
BROWN, EJ ;
ALBERS, MW ;
SHIN, TB ;
ICHIKAWA, K ;
KEITH, CT ;
LANE, WS ;
SCHREIBER, SL .
NATURE, 1994, 369 (6483) :756-758
[5]   CONTROL OF P70 S6 KINASE BY KINASE-ACTIVITY OF FRAP IN-VIVO [J].
BROWN, EJ ;
BEAL, PA ;
KEITH, CT ;
CHEN, J ;
SHIN, TB ;
SCHREIBER, SL .
NATURE, 1995, 377 (6548) :441-446
[6]   Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin [J].
Brunn, GJ ;
Hudson, CC ;
Sekulic, A ;
Williams, JM ;
Hosoi, H ;
Houghton, PJ ;
Lawrence, JC ;
Abraham, RT .
SCIENCE, 1997, 277 (5322) :99-101
[7]   DOMINANT MISSENSE MUTATIONS IN A NOVEL YEAST PROTEIN RELATED TO MAMMALIAN PHOSPHATIDYLINOSITOL 3-KINASE AND VPS34 ABROGATE RAPAMYCIN CYTOTOXICITY [J].
CAFFERKEY, R ;
YOUNG, PR ;
MCLAUGHLIN, MM ;
BERGSMA, DJ ;
KOLTIN, Y ;
SATHE, GM ;
FAUCETTE, L ;
ENG, WK ;
JOHNSON, RK ;
LIVI, GP .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (10) :6012-6023
[8]   Antifungal activities of antineoplastic agents Saccharomyces cerevisiae as a model system to study drug action [J].
Cardenas, ME ;
Cruz, MC ;
Del Poeta, M ;
Chung, NJ ;
Perfect, JR ;
Heitman, J .
CLINICAL MICROBIOLOGY REVIEWS, 1999, 12 (04) :583-+
[9]   IDENTIFICATION OF AN 11-KDA FKBP12-RAPAMYCIN-BINDING DOMAIN WITHIN THE 289-KDA FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN AND CHARACTERIZATION OF A CRITICAL SERINE RESIDUE [J].
CHEN, J ;
ZHENG, XF ;
BROWN, EJ ;
SCHREIBER, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (11) :4947-4951
[10]   RAPT1, A MAMMALIAN HOMOLOG OF YEAST TOR, INTERACTS WITH THE FKBP12 RAPAMYCIN COMPLEX [J].
CHIU, MI ;
KATZ, H ;
BERLIN, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) :12574-12578