Ubiquitin-proteasome-mediated degradation and synthesis of MyoD is modulated by αB-crystallin, a small heat shock protein, during muscle differentiation

Bhairab N. Singh, K. Sridhar Rao, Ch Mohan Rao

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33 Scopus citations

Abstract

αB-crystallin, a small heat shock protein, plays an important role in muscle homeostasis. It gets up-regulated during muscle differentiation and mice lacking αB-crystallin die prematurely with extensive muscle wastage. We have examined the role of αB-crystallin in muscle development using C2C12 myoblasts as a model system. Over-expression of αB-crystallin delays the muscle differentiation program significantly. C2C12 myoblasts over-expressing αB-crystallin (CRYAB-C2C12) display defect in cell-cycle exit upon induction of differentiation. During differentiation, CRYAB-C2C12 cells exhibit sustained level of cyclin D1 and delay in p21 and myogenin expression as compared to C2C12 cells. We find less accumulation of MyoD in CRYAB-C2C12 cells than in C2C12 cells. In vivo protein stability studies reveal faster ubiquitin-proteasome-mediated MyoD degradation in CRYAB-C2C12 cells (t1/2 = 1.42 h) than in C2C12 cells (t1/2 = 2.37 h). Immuno-precipitation experiments showed that MyoD gets ubiquitinated at earlier time points in CRYAB-C2C12 cells than in C2C12 cells. Our data reveal alterations in the synthesis and degradation of MyoD in CRYAB-C2C12 cells. The level of αB-crystallin as well as its Ser-59 phosphorylated form increases with increasing time of differentiation. Our studies show, inter alia, that αB-crystallin modulates myogenesis by altering MyoD level and provide an interesting insight in its role in myogenesis.

Original languageEnglish (US)
Pages (from-to)288-299
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1803
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Cell-cycle
  • Half-life
  • MyoD
  • Myogenesis
  • Ubiquitin
  • sHSPs

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