Regulation of c-Myc protein stability by proteasome activator REGγ

S. Li, C. Jiang, J. Pan, X. Wang, J. Jin, L. Zhao, W. Pan, G. Liao, X. Cai, X. Li, J. Xiao, J. Jiang, P. Wang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

c-Myc is a key transcriptional factor that has a prominent role in cell growth, differentiation and tumor development. Its protein levels are tightly controlled by ubiquitin-proteasome pathway and frequently deregulated in various cancers. Here, we report that the 11S proteasomal activator REGγ is a novel regulator of c-Myc abundance in cells. We showed that overexpression of wild-type REGγ, but not inactive mutants including N151Y and G250S, significantly promoted the degradation of c-Myc. Depletion of REGγ markedly increased the protein stability of c-Myc. REGγ interacts with the C-terminal region of c-Myc and regulates c-Myc protein turnover. Functionally, REGγ negatively regulates c-Myc-mediated cell proliferation. Interestingly, depletion of the Drosophila Reg homolog (dReg) in developing wings induced the upregulation of Drosophila Myc, which contributes to cell death. Collectively, these results suggest that REGγ proteasome has a conserved role in the regulation of Myc abundance in both mammalian cells and Drosophila.

Original languageEnglish (US)
Pages (from-to)1000-1011
Number of pages12
JournalCell Death and Differentiation
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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  • Cite this

    Li, S., Jiang, C., Pan, J., Wang, X., Jin, J., Zhao, L., Pan, W., Liao, G., Cai, X., Li, X., Xiao, J., Jiang, J., & Wang, P. (2015). Regulation of c-Myc protein stability by proteasome activator REGγ. Cell Death and Differentiation, 22(6), 1000-1011. https://doi.org/10.1038/cdd.2014.188