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

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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

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Proto-Oncogene Proteins c-myc
Protein Stability
Proteasome Endopeptidase Complex
Drosophila
Ubiquitin
Cell Differentiation
Neoplasms
Cell Death
Up-Regulation
Cell Proliferation
Growth
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Li, S., Jiang, C., Pan, J., Wang, X., Jin, J., Zhao, L., ... 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

Regulation of c-Myc protein stability by proteasome activator REGγ. / 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.

In: Cell Death and Differentiation, Vol. 22, No. 6, 01.06.2015, p. 1000-1011.

Research output: Contribution to journalArticle

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, vol. 22, no. 6, pp. 1000-1011. https://doi.org/10.1038/cdd.2014.188
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. / Regulation of c-Myc protein stability by proteasome activator REGγ. In: Cell Death and Differentiation. 2015 ; Vol. 22, No. 6. pp. 1000-1011.
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