Jogo Misako, Shiraishi Seiji, Tamura Taka-aki
Department of Biology, Graduate School of Science, Chiba University, Inage-ku, Chiba, Japan.
FEBS Lett. 2009 Sep 3;583(17):2715-9. doi: 10.1016/j.febslet.2009.07.033. Epub 2009 Jul 22.
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.
成肌作用由包括MyoD和肌细胞生成素在内的转录因子介导。已知肌细胞生成素会被SCF（Skp1/Cullin 1/F-box蛋白）多聚泛素化，随后被蛋白酶体降解，不过参与其中的F-box蛋白仍未明确。在本研究中，我们发现分化的成肌细胞中的肌细胞生成素会因诱导肌肉萎缩的地塞米松而变得不稳定，并且在萎缩的肌管中MAFbx（肌肉萎缩F-box蛋白）会增加。MAFbx的过表达导致肌细胞生成素以MG132敏感的方式减少。肌细胞生成素具有MAFbx识别基序并与MAFbx相互作用。MAFbx激活了肌细胞生成素的多聚泛素化。本研究结果表明，MAFbx作为一种F-box蛋白发挥作用，参与肌细胞生成素的泛素化过程。
