Stability of F-box protein atrogin-1 is regulated by p38 mitogen-activated protein kinase pathway in cardiac H9c2 cells

Cell Physiol Biochem. 2011;27(5):463-70. doi: 10.1159/000329967. Epub 2011 Jun 15.


Background: Atrogin-1/MAFbx is a major atrophy-related E3 ubiquitin ligase that functions as a negative regulator of cardiac hypertrophy. The mRNA expression of atrogin-1 is induced by oxidative stress via p38 mitogen-activated protein kinase (p38 MAPK). However, the molecular mechanisms that regulate the stability of atrogin-1 protein remain unclear.

Methods: 293T and cardiac H9c2 cells were transfected with plasmids as indicated. The in vivo and in vitro ubiquitination assay and pulse-chase analysis were performed to detect the ubiquitination and stability of atrogin-1. The protein levels were measured by Western blot analysis.

Results: We found that atrogin-1 underwent ubiquitin-mediated degradation by proteasome. The F-box motif of atrogin-1 and Skp1-Cul1-Roc1-F-box (SCF) complex are required for ubiquitination and degradation of atrogin-1. Furthermore, p38 MAPK signaling plays critical roles in regulating the ubiquitination and degradation of atrogin-1 as well as serum starvation-induced expression of atrogin-1 and reduction of H9c2 cell size.

Conclusion: These findings may define a new mechanism for regulating the stability of atrogin-1 partially by p38 MAPK signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cell Size
  • Cells, Cultured
  • F-Box Motifs*
  • Humans
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Plasmids
  • Protein Binding
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Signal Transduction
  • Transfection
  • Ubiquitin / metabolism*
  • Ubiquitination
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Muscle Proteins
  • Recombinant Proteins
  • Ubiquitin
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • p38 Mitogen-Activated Protein Kinases