Ozz-E3, a muscle-specific ubiquitin ligase, regulates β-catenin degradation during myogenesis

Tommaso Nastasi, Antonella Bongiovanni, Yvan Campos, Linda Mann, James N. Toy, Jake Bostrom, Robbert Rottier, Christopher Hahn, Joan Weliky Conaway, A. John Harris, Alessandra d'Azzo

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The identities of the ubiquitin-ligases active during myogenesis are largely unknown. Here we describe a RING-type E3 ligase complex specified by the adaptor protein, Ozz, a novel SOCS protein that is developmentally regulated and expressed exclusively in striated muscle. In mice, the absence of Ozz results in overt maturation defects of the sarcomeric apparatus. We identified β-catenin as one of the target substrates of the Ozz-E3 in vivo. In the differentiating myofibers, Ozz-E3 regulates the levels of sarcolemma-associated β-catenin by mediating its degradation via the proteasome. Expression of β-catenin mutants that reduce the binding of Ozz to endogenous β-catenin leads to Mb-β-catenin accumulation and myofibrillogenesis defects similar to those observed in Ozz null myocytes. These findings reveal a novel mechanism of regulation of Mb-β-catenin and the role of this pool of the protein in myofibrillogenesis, and implicate the Ozz-E3 ligase in the process of myofiber differentiation.

Original languageEnglish (US)
Pages (from-to)269-282
Number of pages14
JournalDevelopmental cell
Volume6
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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