title: SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Ser62.
abstract: Serine 62 (Ser62) phosphorylation affects the c-Myc protein stability in cancer cells. However, the mechanism for dephosphorylating c-Myc is not well understood. In this study, we identified carboxyl-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (SCP1) as a novel phosphatase specifically dephosphorylating c-Myc Ser62. Ectopically expressed SCP1 strongly dephosphorylated c-Myc Ser62, destabilized c-Myc protein and suppressed c-Myc transcriptional activity. Knockdown of SCP1 increased the c-Myc protein levels in liver cancer cells. SCP1 interacted with c-Myc both in vivo and in vitro. In addition, Ser245 at the C-terminus of SCP1 was essential for its phosphatase activity towards c-Myc. Functionally, SCP1 negatively regulated the cancer cell proliferation. Collectively, our findings indicate that SCP1 is a potential tumor suppressor for liver cancers through dephosphorylating c-Myc Ser62.
authors.affiliation: Department of Central Laboratory, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Liao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Shen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Central Laboratory, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Central Laboratory, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.|School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012694:Serine; C413483:CTDSP1 protein, human; D010749:Phosphoprotein Phosphatases; C000608368:Scp1 protein, mouse