Regulation of c-Myc protein stability by proteasome activator REGγ

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 REG gamma is a novel regulator of c-Myc abundance in cells. We showed that overexpression of wild-type REG gamma, but not inactive mutants including N151Y and G250S, significantly promoted the degradation of c-Myc. Depletion of REG gamma markedly increased the protein stability of c-Myc. REG gamma interacts with the C-terminal region of c-Myc and regulates c-Myc protein turnover. Functionally, REG gamma 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 REG gamma proteasome has a conserved role in the regulation of Myc abundance in both mammalian cells and Drosophila.