Nek5, a novel substrate for caspase-3, promotes skeletal muscle differentiation by up-regulating caspase activity

FEBS Lett. 2013 Jul 11;587(14):2219-25. doi: 10.1016/j.febslet.2013.05.049. Epub 2013 May 31.

Abstract

Accumulating evidence suggests that caspase-3-mediated cleavage of protein kinase could be a key event to regulate cell differentiation. In this study, we investigated the role of Nek5 kinase, identified as a novel substrate for caspase-3, in skeletal muscle differentiation. Up-regulation of Nek5 mRNA expression was accompanied by cell differentiation. Myotube formation was promoted in Nek5 expressing cells, and was conversely inhibited in Nek5 knockdown cells. Furthermore, we found that caspase-3 activity, an important factor for myogenic differentiation, was enhanced by Nek5 cleavage. Although caspase-3-cleaved Nek5 partially exerted a promyogenic effect, it tended to induce apoptotic cell death. In summary, our findings suggest that Nek5 promotes myogenic differentiation through up-regulation of caspase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Caspase 3 / chemistry
  • Caspase 3 / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Enzyme Induction
  • Mice
  • Muscle Development
  • Myoblasts / physiology*
  • NIMA-Related Kinases
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Up-Regulation*

Substances

  • RNA, Messenger
  • Protein Kinases
  • NIMA-Related Kinases
  • Nek5 protein, mouse
  • Casp3 protein, mouse
  • Caspase 3