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ABSTRACT

Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.

Subject(s)

DNA-Binding Proteins , Gene Expression Profiling , Muscle, Skeletal/metabolism , Muscular Atrophy/genetics , Peptide Synthases/metabolism , Trans-Activators , Amino Acid Sequence , Animals , Cloning, Molecular , Creatine Kinase/genetics , Creatine Kinase, MM Form , Gene Deletion , Hindlimb Suspension , Humans , Immobilization , Isoenzymes/genetics , Mice , Mice, Knockout , Molecular Sequence Data , Muscle Denervation , Muscle Proteins/genetics , Muscle, Skeletal/growth & development , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , MyoD Protein/genetics , Myogenic Regulatory Factor 5 , Myogenin/genetics , Peptide Synthases/chemistry , Peptide Synthases/deficiency , Peptide Synthases/genetics , Phenotype , Protein Binding , RNA, Messenger/analysis , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , SKP Cullin F-Box Protein Ligases , Up-Regulation

ABSTRACT

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