title: eIF3f: a central regulator of the antagonism atrophy/hypertrophy in skeletal muscle.
abstract: The eukaryotic initiation factor 3 subunit f (eIF3f) is one of the 13 subunits of the translation initiation factor complex eIF3 required for several steps in the initiation of mRNA translation. In skeletal muscle, recent studies have demonstrated that eIF3f plays a central role in skeletal muscle size maintenance. Accordingly, eIF3f overexpression results in hypertrophy through modulation of protein synthesis via the mTORC1 pathway. Importantly, eIF3f was described as a target of the E3 ubiquitin ligase MAFbx/atrogin-1 for proteasome-mediated breakdown under atrophic conditions. The biological importance of the MAFbx/atrogin-1-dependent targeting of eFI3f is highlighted by the finding that expression of an eIF3f mutant insensitive to MAFbx/atrogin-1 polyubiquitination is associated with enhanced protection against starvation-induced muscle atrophy. A better understanding of the precise role of this subunit should lead to the development of new therapeutic approaches to prevent or limit muscle wasting that prevails in numerous physiological and pathological states such as immobilization, aging, denervated conditions, neuromuscular diseases, AIDS, cancer, diabetes. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
authors.affiliation: INRA, UMR866, Université Montpellier 1, Université Montpellier 2, 2 Place Viala, 34060 Montpellier, France.
authors.forename: Anthony M J
authors.initials: AM
authors.lastname: Sanchez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Csibi
authors.forename: Audrey
authors.initials: A
authors.lastname: Raibon
authors.forename: Aurélie
authors.initials: A
authors.lastname: Docquier
authors.forename: Julie
authors.initials: J
authors.lastname: Lagirand-Cantaloube
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Leibovitch
authors.forename: Serge A
authors.initials: SA
authors.lastname: Leibovitch
authors.forename: Henri
authors.initials: H
authors.lastname: Bernardi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D015398:Signal Transduction
chemical_list: D039621:Eukaryotic Initiation Factor-3; D009124:Muscle Proteins
keywords: Cell growth; MAFbx/atrogin-1; Protein translation; Skeletal muscle; eIF3f