Mitsugumin 53 (MG53) Ligase ubiquitinates Focal Adhesion Kinase during Skeletal Myogenesis

Nga Nguyen, Jae Sung Yi, Heonyong Park, Jae Seon Lee, Young Gyu Ko

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Background: The FAK protein level decreases, but itsmRNAlevel remains constant, during skeletal myogenesis, suggesting that an E3 ligase could induce FAK ubiquitination. Results: The E3 ligase MG53 induces FAK ubiquitination and degradation. Conclusion: MG53-mediated FAK ubiquitination and degradation is induced during myogenesis. Significance: This work provides a molecular mechanism for the negative feedback regulation of skeletal myogenesis. The striated muscle-specific mitsugumin 53 (MG53) is a novel E3 ligase that induces the ubiquitination of insulin receptor substrate 1 (IRS-1) during skeletal myogenesis, negatively regulating insulin-like growth factor and insulin signaling. Here we show that focal adhesion kinase (FAK) is the second target of MG53 during skeletal myogenesis. The FAK protein level gradually decreased, whereas its mRNA level was constant during myogenesis in C2C12 cells and MyoD-overexpressing mouse embryonic fibroblasts. The FAK protein was associated with the E2 enzymeUBE2Hand the E3 enzymeMG53in endogenous and exogenous immunoprecipitation experiments. FAK ubiquitination and degradation was induced by MG53 overexpression in myoblasts but abolished by MG53 or UBE2H knockdown in myotubes. Because RING-disrupted MG53 mutants (C14A and δR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53-induced FAK ubiquitination. Taken together, these data indicate that MG53 induces FAK ubiquitination with the aid of UBE2H during skeletal myogenesis.

Original languageEnglish
Pages (from-to)3209-3216
Number of pages8
JournalJournal of Biological Chemistry
Issue number6
Publication statusPublished - 2014 Feb 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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