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论文题目: SUMOylation and SENP3 regulate STAT3 activation in head and neck cancer
英文论文题目: SUMOylation and SENP3 regulate STAT3 activation in head and neck cancer
第一作者: Zhou, Z; Wang, M; Li, J; Xiao, M; Chin, YE; Cheng, J; Yeh, ETH; Yang, J; Yi, J
英文第一作者: Zhou, Z; Wang, M; Li, J; Xiao, M; Chin, YE; Cheng, J; Yeh, ETH; Yang, J; Yi, J
联系作者: Yang, J; Yi, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Biochem & Mol Cell Biol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China.
英文联系作者: Yang, J; Yi, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Biochem & Mol Cell Biol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China.
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发表年度: 2016
卷: 35
期: 45
页码: 5826-5838
摘要: Hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including head and neck cancer (HNC). Although smoking is critical in the development and progression of HNC, how tobacco components activate STAT3 is unclear. We demonstrated that exposure of HNC cell lines to a tobacco extract induced a rapid Y705 phosphorylation of STAT3 and a rapid increase in the SUMO protease SENP3 that depended on a simultaneous increase in reactive oxygen species. We identified that SUMOylation at the lysine 451 site facilitated STAT3 binding to the phosphatase TC45 through an SUMO-interacting motif of TC45. SENP3 could thus enhance STAT3 phosphorylation by de-conjugating the SUMO2/3 modification of STAT3. Knocking-down of SENP3 greatly impaired basal and induced STAT3 phosphorylation by tobacco extract or interleukin 6. A correlation between SENP3 protein levels and STAT3 Y705 phosphorylation levels in human laryngeal carcinoma specimens was found, which was more significant in the specimens derived from the smoker patients and with poor clinicopathological parameters. Our data identified SUMOylation as a previously undescribed post-translational modification of STAT3 and SENP3 as a critical positive modulator of tobacco-or cytokine-induced STAT3 activation. These findings provide novel insights into the hyperphosphorylation of STAT3 in development of HNC.
英文摘要: Hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including head and neck cancer (HNC). Although smoking is critical in the development and progression of HNC, how tobacco components activate STAT3 is unclear. We demonstrated that exposure of HNC cell lines to a tobacco extract induced a rapid Y705 phosphorylation of STAT3 and a rapid increase in the SUMO protease SENP3 that depended on a simultaneous increase in reactive oxygen species. We identified that SUMOylation at the lysine 451 site facilitated STAT3 binding to the phosphatase TC45 through an SUMO-interacting motif of TC45. SENP3 could thus enhance STAT3 phosphorylation by de-conjugating the SUMO2/3 modification of STAT3. Knocking-down of SENP3 greatly impaired basal and induced STAT3 phosphorylation by tobacco extract or interleukin 6. A correlation between SENP3 protein levels and STAT3 Y705 phosphorylation levels in human laryngeal carcinoma specimens was found, which was more significant in the specimens derived from the smoker patients and with poor clinicopathological parameters. Our data identified SUMOylation as a previously undescribed post-translational modification of STAT3 and SENP3 as a critical positive modulator of tobacco-or cytokine-induced STAT3 activation. These findings provide novel insights into the hyperphosphorylation of STAT3 in development of HNC.
刊物名称: ONCOGENE
英文刊物名称: ONCOGENE
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学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
英文学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
影响因子: 7.519
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论文类别: Article
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