4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle

Maintenance of cellular protein stores in skeletal muscle depends on a tigh tly regulated synthesis-degradation equilibrium that is conditionally modul ated under an extensive range of physiological and pathophysiological circu mstances. Recent studies have established the initiation phase of mRNA tran slation as a pivotal site of regulation for global rates of protein synthes is, as well as a site through which the synthesis of specific proteins is c ontrolled. The protein synthetic pathway is exquisitely sensitive to the av ailability of hormones and nutrients and employs a comprehensive integrativ e strategy to interpret the information provided by hormonal and nutritiona l cues. The translational repressor, eukaryotic initiation factor 4E bindin g protein 1 (4E-BP1), and the 70-kDa ribosomal protein S6 kinase (S6K1) hav e emerged as important components of this strategy, and together they coord inate 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 cha nges in mRNA translation through the influence of these translational effec tors.