Identification of MAFbx as a myogenin-engaged F-box protein in SCF ubiquitin ligase

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 summaryMINT-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)