Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation

被引:236
作者
Dennis, PB [1 ]
Fumagalli, S [1 ]
Thomas, G [1 ]
机构
[1] Friedrich Miescher Inst, CH-4058 Basel, Switzerland
关键词
D O I
10.1016/S0959-437X(99)80007-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mitogenic and nutritional signals must be integrated for a cell to grow. The target of rapamycin (TOR) is emerging as an effector for signals which indicate to the cell whether the external environment is conducive for growth. Use of the, immunosuppressant rapamycin, a bacterial macrolide, has been instructive in identifying potential signaling components downstream of TOR, leading to the observation that both protein synthesis and turnover are under TOR control. The central issues concerning TOR are the identification of the proliferative and anti-proliferative signals which mediate its function and the mechanisms by which these signals are transduced to downstream molecules.
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页码:49 / 54
页数:6
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共 53 条
[1]   Atypical protein kinase Cλ binds and regulates p70 S6 kinase [J].
Akimoto, K ;
Nakaya, M ;
Yamanaka, T ;
Tanaka, J ;
Matsuda, S ;
Weng, QP ;
Avruch, J ;
Ohno, S .
BIOCHEMICAL JOURNAL, 1998, 335 :417-424
[2]   A novel inhibitor of cap-dependent translation initiation in yeast: P20 competes with eIF4G for binding to eIF4E [J].
Altmann, M ;
Schmitz, N ;
Berset, C ;
Trachsel, H .
EMBO JOURNAL, 1997, 16 (05) :1114-1121
[3]   HEAT REPEATS IN THE HUNTINGTONS-DISEASE PROTEIN [J].
ANDRADE, MA ;
BORK, P .
NATURE GENETICS, 1995, 11 (02) :115-116
[4]   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
[5]   cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells [J].
Begum, N ;
Ragolia, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (49) :31166-31171
[6]   Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation [J].
Beretta, L ;
Gingras, AC ;
Svitkin, YV ;
Hall, MN ;
Sonenberg, N .
EMBO JOURNAL, 1996, 15 (03) :658-664
[7]   The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae [J].
Berset, C ;
Trachsel, H ;
Altmann, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4264-4269
[8]   PHOSPHORYLATION OF RIBOSOMAL-PROTEIN S6 IS INHIBITORY FOR AUTOPHAGY IN ISOLATED RAT HEPATOCYTES [J].
BLOMMAART, EFC ;
LUIKEN, JJFP ;
BLOMMAART, PJE ;
VANWOERKOM, GM ;
MEIJER, AJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (05) :2320-2326
[9]   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
[10]   The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus [J].
Brunn, GJ ;
Fadden, P ;
Haystead, TAJ ;
Lawrence, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (51) :32547-32550