eIF3-f function in skeletal muscles: to stand at the crossroads of atrophy and hypertrophy.

Abstract

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.

• Authors: Alfredo Csibi, Lionel A Tintignac, Marie Pierre Leibovitch, Serge A Leibovitch
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 7 Issue 12 Pg. 1698-701 (Jun 15 2008) ISSN: 1551-4005 [Electronic] United States
• PMID: 18583931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eukaryotic Initiation Factor-3
• Muscle Proteins
• Protein Subunits
• Fbxo32 protein, mouse
• SKP Cullin F-Box Protein Ligases
• Protein Kinases
• MTOR protein, human
• mTOR protein, mouse
• Ribosomal Protein S6 Kinases
• TOR Serine-Threonine Kinases

Topics

• Animals
• Eukaryotic Initiation Factor-3 (antagonists & inhibitors, chemistry, physiology)
• Humans
• Hypertrophy
• Muscle Proteins (chemistry, metabolism)
• Muscle, Skeletal (growth & development, metabolism, pathology)
• Muscular Atrophy (etiology, genetics, metabolism)
• Protein Biosynthesis
• Protein Kinases (metabolism)
• Protein Subunits (physiology)
• Ribosomal Protein S6 Kinases (metabolism)
• SKP Cullin F-Box Protein Ligases (chemistry, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases
• Wasting Syndrome (therapy)