Identification of MAFbx as a myogenin-engaged F-box protein in SCF ubiquitin ligase
Abstract
Myogenesis is conducted by transcription factors including MyoD and myogenin. Myogenin is known to be polyubiquitinated by SCF (Skp1/Cullin 1/F-box protein) followed by proteasomal degradation, though the participating F-box protein is remaining unidentified. In this study, we found that myogenin in differentiated myoblasts is destabilized by muscle atrophy-inducing dexamethasone and that MAFbx (muscle atrophy F-box protein) is increased in atrophying myotubes. MAFbx overexpression resulted in MG132-sensitive reduction of myogenin. Myogenin had a MAFbx-recognition motif and interacted with MAFbx. MAFbx activated polyubiquitination of myogenin. The results of this study suggest that MAFbx functions as an F-box protein for ubiquitination of myogenin.
Structured summary
MINT-7222713: Myogenin (uniprotkb:P12979) physically interacts (MI:0914) with MAFbx (uniprotkb:Q9CPU7) by anti tag coimmunoprecipitation (MI:0007)
MINT-7222741: Myogenin (uniprotkb:P12979) physically interacts (MI:0914) with MAFbx (uniprotkb:Q9CPU7) by anti bait coimmunoprecipitation (MI:0006)
MINT-7222726: Myogenin (uniprotkb:P12979) and MAFbx (uniprotkb:Q9CPU7) colocalize (MI:0403) by fluorescence microscopy (MI:0416)
MINT-7222760: Myogenin (uniprotkb:P12979) physically interacts (MI:0914) with Ubiquitin (uniprotkb:P62991) by anti bait coimmunoprecipitation (MI:0006)
Abbreviations: UPS, ubiquitin proteasome system, Ub, ubiquitin, MAFbx, muscle atrophy F-box protein, SCF, Skp1/Cullin 1/F-box protein, MuRF1, muscle RING-finger protein-1, Dex, dexamethasone, IGF-1, insulin-like growth factor-1, HA, hemagglutinin, siRNA, small interference RNA, GM, growth medium, DM, differentiation medium, PAGE, polyacrylamide gel electrophoresis, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, TBP, TATA-binding protein
Keywords: MAFbx, Atrogin-1, Ubiquitination, Myogenin, Myogenesis, SCF
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PII: S0014-5793(09)00559-6
doi:10.1016/j.febslet.2009.07.033
© 2009 Federation of European Biochemical Societies. Published by Elsevier BV. All rights reserved.
