Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation

Aldrin V Gomes, Dave S. Waddell, Rylie Siu, Matthew Stein, Shannamar Dewey, John Furlow, Sue C. Bodine

Research output: Contribution to journalArticle

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2986-2999
Number of pages14
JournalFASEB Journal
Volume26
Issue number7
DOIs
StatePublished - Jul 2012

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Keywords

  • E3 ubiquitin ligase
  • MAFbx
  • Muscle atrophy
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Gomes, A. V., Waddell, D. S., Siu, R., Stein, M., Dewey, S., Furlow, J., & Bodine, S. C. (2012). Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation. FASEB Journal, 26(7), 2986-2999. https://doi.org/10.1096/fj.12-204495