title: Regulation of c-Myc protein stability by proteasome activator REGγ.
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.
authors.affiliation: 1] Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China [2] Department of Developmental Biology, UT Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: 1] Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China [2] Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Liao
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Developmental Biology, UT Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.affiliation: 1] Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China [2] Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004330:Drosophila; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D016271:Proto-Oncogene Proteins c-myc; D046988:Proteasome Endopeptidase Complex