TY - JOUR
T1 - Regulation of c-Myc protein stability by proteasome activator REGγ
AU - Li, S.
AU - Jiang, C.
AU - Pan, J.
AU - Wang, X.
AU - Jin, J.
AU - Zhao, L.
AU - Pan, W.
AU - Liao, G.
AU - Cai, X.
AU - Li, X.
AU - Xiao, J.
AU - Jiang, J.
AU - Wang, P.
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.1038/cdd.2014.188
DO - 10.1038/cdd.2014.188
M3 - Article
C2 - 25412630
AN - SCOPUS:84939987834
SN - 1350-9047
VL - 22
SP - 1000
EP - 1011
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 6
ER -