Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes

被引:53
作者
Tinton, SA [1 ]
Buc-Calderon, PM [1 ]
机构
[1] Univ Catholique Louvain, Unite Biochim Toxicol & Cancerol, B-1200 Brussels, Belgium
来源
FEBS LETTERS | 1999年 / 446卷 / 01期
关键词
hypoxia; protein synthesis; phosphoprotein heat- and acid-stable induced by insulin; eukaryotic initiation factor;
D O I
10.1016/S0014-5793(99)00185-4
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
Incubation of hepatocytes under hypoxia increases binding of translation initiation factor eIF-4E to its inhibitory regulator 4E-BP1, and this correlates with dephosphorylation of 4E-BP1. Rapamycin induced the same effect in aerobic cells but no additive effect was observed when hypoxic cells were treated with rapamycin. This enhanced association of 4E-BP1 with eIF-4E might be mediated by mTOR. Nevertheless, only hypoxia produces a rapid inhibition of protein synthesis. Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia. (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:55 / 59
页数:5
相关论文
共 33 条
[1]   A signaling pathway to translational control [J].
Brown, EJ ;
Schreiber, SL .
CELL, 1996, 86 (04) :517-520
[2]   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
[3]   Oxygen sensing and molecular adaptation to hypoxia [J].
Bunn, HF ;
Poyton, RO .
PHYSIOLOGICAL REVIEWS, 1996, 76 (03) :839-885
[4]   RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 [J].
Burnett, PE ;
Barrow, RK ;
Cohen, NA ;
Snyder, SH ;
Sabatini, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (04) :1432-1437
[5]   Both rapamycin-sensitive and -insensitive pathways are involved in the phosphorylation of the initiation factor-4E-binding protein (4E-BP1) in response to insulin in rat epididymal fat-cells [J].
Diggle, TA ;
Moule, SK ;
Avison, MB ;
Flynn, A ;
Foulstone, EJ ;
Proud, CG ;
Denton, RM .
BIOCHEMICAL JOURNAL, 1996, 316 :447-453
[6]  
FREIGENBLUM D, 1996, MOL CELL BIOL, V16, P5450
[7]   4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway [J].
Gingras, AC ;
Kennedy, SG ;
O'Leary, MA ;
Sonenberg, N ;
Hay, N .
GENES & DEVELOPMENT, 1998, 12 (04) :502-513
[8]   CAMP-SENSITIVE AND RAPAMYCIN-SENSITIVE REGULATION OF THE ASSOCIATION OF EUKARYOTIC INITIATION-FACTOR 4E AND THE TRANSLATIONAL REGULATOR PHAS-I IN AORTIC SMOOTH-MUSCLE CELLS [J].
GRAVES, LM ;
BORNFELDT, KE ;
ARGAST, GM ;
KREBS, EG ;
KONG, XM ;
LIN, TA ;
LAWRENCE, JC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7222-7226
[9]   REPRESSION OF CAP-DEPENDENT TRANSLATION BY 4E-BINDING PROTEIN-1 - COMPETITION WITH P220 FOR BINDING TO EUKARYOTIC INITIATION FACTOR-4E [J].
HAGHIGHAT, A ;
MADER, S ;
PAUSE, A ;
SONENBERG, N .
EMBO JOURNAL, 1995, 14 (22) :5701-5709
[10]   Regulation of eIF-4E BP1 phosphorylation by mTOR [J].
Hara, K ;
Yonezawa, K ;
Kozlowski, MT ;
Sugimoto, T ;
Andrabi, K ;
Weng, QP ;
Kasuga, M ;
Nishimoto, I ;
Avruch, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (42) :26457-26463