Regulation of c-Myc protein stability by proteasome activator REGγ
| Autor: | L. Zhao, Xiaotao Li, Ping Wang, J. Pan, W Pan, Jin Jiang, Xiaoshuang Wang, J. Jin, Jianru Xiao, C. Jiang, G. Liao, X. Cai, S. Li |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
Original Paper Programmed cell death Protein Stability Cell growth Activator (genetics) Blotting Western Protein turnover Cell Biology Biology Autoantigens Cell Line Cell biology Proto-Oncogene Proteins c-myc Proteasome Downregulation and upregulation Cell culture RNA interference Cancer research Animals Humans Drosophila RNA Interference Molecular Biology |
| Zdroj: | Cell Death & Differentiation. 22:1000-1011 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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