title: Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation.
abstract: Deletion of muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, leads to sparing of muscle mass following denervation. The purpose of this study was to test the hypothesis that muscle sparing in mice with a deletion of MuRF1 is due to the selective inhibition of the ubiquitin proteasome system. Activities of the 20S and 26S proteasomes, calpain and cathepsin L, were measured in the triceps surae muscles of wild-type (WT) and MuRF1-knockout (KO) mice at 3 and 14 d following denervation. In addition, fractional protein synthesis rates and differential gene expression were measured in WT and KO muscle. The major finding was that 20S and 26S proteasome activities were significantly elevated (1.5- to 2.5-fold) after 14 d of denervation in both WT and KO mice relative to control, but interestingly, the activities of both the 20S and 26S proteasome were significantly higher in KO than WT mice. Further, mRNA expression of MAFbx was elevated after 14 d of denervation in KO, but not WT, mice. These data challenge the conventional dogma that MuRF1 is controlling the degradation of only contractile proteins and suggest a role for MuRF1 in the global control of the ubiquitin proteasome system and protein turnover.
authors.affiliation: Department of Physiology, Neurobiology and Behavior, and University of California, Davis, California 95616, USA.
authors.forename: Aldrin V
authors.initials: AV
authors.lastname: Gomes
authors.forename: Dave S
authors.initials: DS
authors.lastname: Waddell
authors.forename: Rylie
authors.initials: R
authors.lastname: Siu
authors.forename: Matthew
authors.initials: M
authors.lastname: Stein
authors.forename: Shannamar
authors.initials: S
authors.lastname: Dewey
authors.forename: J David
authors.initials: JD
authors.lastname: Furlow
authors.forename: Sue C
authors.initials: SC
authors.lastname: Bodine
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D002154:Calpain / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D005260:Female; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009121:Muscle Denervation; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000172:deficiency / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D029681:Arabidopsis Proteins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D002154:Calpain; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis