UBE2C promotes myoblast differentiation and skeletal muscle regeneration through the Akt signaling pathway

Acta Biochim Biophys Sin (Shanghai). 2024 Apr 29;56(7):1065-1071. doi: 10.3724/abbs.2024062.

Abstract

Ubiquitin-conjugation enzyme E2C (UBE2C) is a crucial component of the ubiquitin-proteasome system that is involved in numerous cancers. In this study, we find that UBE2C expression is significantly increased in mouse embryos, a critical stage during skeletal muscle development. We further investigate the function of UBE2C in myogenesis. Knockdown of UBE2C inhibits C2C12 cell differentiation and decreases the expressions of MyoG and MyHC, while overexpression of UBE2C promotes C2C12 cell differentiation. Additionally, knockdown of UBE2C, specifically in the tibialis anterior muscle (TA), severely impedes muscle regeneration in vivo. Mechanistically, we show that UBE2C knockdown reduces the level of phosphorylated protein kinase B (p-Akt) and promotes the degradation of Akt. These findings suggest that UBE2C plays a critical role in myoblast differentiation and muscle regeneration and that UBE2C regulates myogenesis through the Akt signaling pathway.

Keywords: Akt; UBE2C; muscle; myoblast differentiation.

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line
  • Mice
  • Muscle Development* / genetics
  • Muscle, Skeletal* / cytology
  • Muscle, Skeletal* / metabolism
  • Myoblasts* / cytology
  • Myoblasts* / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Regeneration* / genetics
  • Signal Transduction*
  • Ubiquitin-Conjugating Enzymes* / genetics
  • Ubiquitin-Conjugating Enzymes* / metabolism

Substances

  • Ubiquitin-Conjugating Enzymes
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 32072697), the Rural Revitalization Special Project of Guangdong Province (No. 2021-440000-24010202-8887), the Laboratory of Lingnan Modern Agriculture Project (No. NZ2021006), and the Earmarked Fund for CARS-35.