ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation

Sci Rep. 2021 Oct 22;11(1):20880. doi: 10.1038/s41598-021-00306-6.


Cell adhesion molecule-related/downregulated by oncogenes (Cdon) is a cell-surface receptor that mediates cell-cell interactions and positively regulates myogenesis. The cytoplasmic region of Cdon interacts with other proteins to form a Cdon/JLP/Bnip-2/CDC42 complex that activates p38 mitogen-activated protein kinase (MAPK) and induces myogenesis. However, Cdon complex may include other proteins during myogenesis. In this study, we found that Cullin 2-interacting protein zinc finger SWIM type containing 8 (ZSWIM8) ubiquitin ligase is induced during C2C12 differentiation and is included in the Cdon complex. We knocked-down Zswim8 in C2C12 cells to determine the effect of ZSWIM8 on differentiation. However, we detected neither ZSWIM8-dependent ubiquitination nor the degradation of Bnip2, Cdon, or JLP. In contrast, ZSWIM8 knockdown accelerated C2C12 differentiation. These results suggest that ZSWIM8 is a Cdon complex-included myogenic protein that prevents C2C12 differentiation without affecting the stability of Bnip2, Cdon, and JLP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation / physiology*
  • Cell Line
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • K562 Cells
  • MAP Kinase Signaling System / physiology
  • Muscle Development / physiology*
  • Protein Binding / physiology
  • Ubiquitin-Protein Ligases / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Cell Adhesion Molecules
  • Ubiquitin-Protein Ligases
  • ZSWIM8 protein, human
  • p38 Mitogen-Activated Protein Kinases