4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle
Open Access
- 1 October 2000
- journal article
- review article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 279 (4) , E715-E729
- https://doi.org/10.1152/ajpendo.2000.279.4.e715
Abstract
Maintenance of cellular protein stores in skeletal muscle depends on a tightly regulated synthesis-degradation equilibrium that is conditionally modulated under an extensive range of physiological and pathophysiological circumstances. Recent studies have established the initiation phase of mRNA translation as a pivotal site of regulation for global rates of protein synthesis, as well as a site through which the synthesis of specific proteins is controlled. The protein synthetic pathway is exquisitely sensitive to the availability of hormones and nutrients and employs a comprehensive integrative strategy to interpret the information provided by hormonal and nutritional cues. The translational repressor, eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and the 70-kDa ribosomal protein S6 kinase (S6K1) have emerged as important components of this strategy, and together they coordinate the behavior of both eukaryotic initiation factors and the ribosome. This review discusses the role of 4E-BP1 and S6K1 in translational control and outlines the mechanisms through which hormones and nutrients effect changes in mRNA translation through the influence of these translational effectors.Keywords
This publication has 126 references indexed in Scilit:
- Multiple Mechanisms Control Phosphorylation of PHAS-I in Five (S/T)P Sites That Govern Translational RepressionMolecular and Cellular Biology, 2000
- Ribosomal S6 Kinase Signaling and the Control of TranslationExperimental Cell Research, 1999
- Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteersThe Journal of Nutritional Biochemistry, 1999
- Expression, Enzyme Activity, and Subcellular Localization of Mammalian Target of Rapamycin in Insulin-Responsive CellsBiochemical and Biophysical Research Communications, 1997
- Expression and Chromosomal Localization of the Human α4/IGBP1 Gene, the Structure of Which Is Closely Related to the Yeast TAP42 Protein of the Rapamycin-Sensitive Signal Transduction PathwayGenomics, 1997
- Modulation of Translation Initiation in Rat Skeletal Muscle and Liver in Response to Food IntakeBiochemical and Biophysical Research Communications, 1997
- Specific Increase in p85α Expression in Response to Dexamethasone Is Associated with Inhibition of Insulin-like Growth Factor-I Stimulated Phosphatidylinositol 3-Kinase Activity in Cultured Muscle CellsPublished by Elsevier ,1997
- Tissue Distribution, Genomic Structure, and Chromosome Mapping of Mouse and Human Eukaryotic Initiation Factor 4E-Binding Proteins 1 and 2Genomics, 1996
- The Rapamycin and FKBP12 Target (RAFT) Displays Phosphatidylinositol 4-Kinase ActivityPublished by Elsevier ,1995
- Activation of p70/p85 S6 kinase by a pathway independent of p21fi rasNature, 1994