eIF3-f function in skeletal muscles: to stand at the crossroads of atrophy and hypertrophy.
The control of muscle cell size is a physiological process balanced by a fine tuning between protein synthesis and protein degradation. MAFbx/Atrogin-1 is a muscle specific E3 ubiquitin ligase upregulated during disuse, immobilization and fasting or systemic diseases such as diabetes, cancer, AIDS and renal failure. This response is necessary to induce a rapid and functional atrophy. To date, the targets of MAFbx/Atrogin-1 in skeletal muscle remain to be identified. We have recently presented evidence that eIF3-f, a regulatory subunit of the eukaryotic translation factor eIF3 is a key target that accounts for MAFbx/Atrogin-1 function in muscle atrophy. More importantly, we showed that eIF3-f acts as a "translational enhancer" that increases the efficiency of the structural muscle proteins synthesis leading to both in vitro and in vivo muscle hypertrophy. We propose that eIF3-f subunit, a mTOR/S6K1 scaffolding protein in the IGF-1/Akt/mTOR dependent control of protein translation, is a positive actor essential to the translation of specific mRNAs probably implicated in muscle hypertrophy. The central role of eIF3-f in both the atrophic and hypertrophic pathways will be discussed in the light of its promising potential in muscle wasting therapy.
Csibi
Alfredo
A
Laboratoire de Génomique Fonctionnelle et Myogenèse, UMR866 Différenciation Cellulaire et Croissance, INRA UM II, Campus INRA/SUPAGRO, Montpellier, France.
Tintignac
Lionel A
LA
Leibovitch
Marie Pierre
MP
Leibovitch
Serge A
SA
D000818:Animals; D039621:Eukaryotic Initiation Factor-3 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D019282:Wasting Syndrome / Q000628:therapy
D039621:Eukaryotic Initiation Factor-3; D009124:Muscle Proteins; D021122:Protein Subunits; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases