Wang W, Liao P, Shen M, Chen T, Chen Y, Li Y, Lin X, Ge X, Wang P
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.
Oncogene. 2016 Jan 28;35(4):491-500. doi: 10.1038/onc.2015.106. Epub 2015 Apr 20.
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.
丝氨酸62（Ser62）磷酸化影响癌细胞中c-Myc蛋白的稳定性。然而，c-Myc去磷酸化的机制尚不清楚。在本研究中，我们鉴定出羧基末端结构域RNA聚合酶II多肽A小磷酸酶1（SCP1）是一种特异性使c-Myc Ser62去磷酸化的新型磷酸酶。异位表达的SCP1强烈使c-Myc Ser62去磷酸化，使c-Myc蛋白不稳定并抑制c-Myc转录活性。敲低SCP1可增加肝癌细胞中c-Myc蛋白水平。SCP1在体内和体外均与c-Myc相互作用。此外，SCP1 C末端的丝氨酸245对其针对c-Myc的磷酸酶活性至关重要。在功能上，SCP1负向调节癌细胞增殖。总体而言，我们的研究结果表明，SCP1通过使c-Myc Ser62去磷酸化而成为肝癌的潜在肿瘤抑制因子。
