Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise.
Control of translation initiation in a tissue of an intact mammalian organism is a highly complex process requiring the continuous integration of multiple positive and negative stimuli. For a tissue such as skeletal muscle, which has the capacity to undergo dramatic changes in size and protein content, translation initiation contributes importantly to the regulation of global rates of protein synthesis and is controlled by numerous stimuli, including those arising from nutrients and hormones in the circulating blood, as well as from contraction-induced signaling within the tissue. Many of the pathways conveying signals generated by these stimuli converge on mTORC1, a serine-threonine protein kinase that has been termed the nutrient and energy sensor of the cell and that plays a prominent role in the regulation of cell growth. Control of translation initiation by mTORC1 is mediated through phosphorylation of downstream targets that modulate the binding of mRNA to the 43 S preinitiation complex. Control of translation initiation is also mediated through modulation of binding of initiator methionyl-tRNA to the 40 S ribosomal subunit. Together, modulation of these two regulatory steps in translation initiation accounts in large part for changes in protein synthesis in skeletal muscle produced by the integration of inputs from hormones, nutrients, and exercise.
Kimball
Scot R
SR
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. skimball@psu.edu
Jefferson
Leonard S
LS
D000818:Animals; D015444:Exercise / Q000502:physiology*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D018482:Muscle, Skeletal / Q000378:metabolism; D011506:Proteins; D012358:RNA, Transfer, Met / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
D006728:Hormones; C112736:Met-tRNA(i)(Met); D046912:Multiprotein Complexes; D011506:Proteins; D012358:RNA, Transfer, Met; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases