14-3-3 zeta Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells
文献类型:期刊论文
作者 | Zhang, Jia1; Chen, Fangjin2; Li, Wenliang3; Xiong, Qian1; Yang, Mingkun1; Zheng, Peng1; Li, Chongyang1; Pei, Jianfeng2; Ge, Feng1 |
刊名 | PLOS ONE
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出版日期 | 2012-01-18 |
卷号 | 7期号:1页码:e29554 |
ISSN号 | 1932-6203 |
通讯作者 | Zhang, J (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China |
中文摘要 | The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3 zeta, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3 zeta interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3 zeta interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3 zeta interaction and mutation of Ser727 to Alanine abolished 14-3-3 zeta/Stat3 association. Inhibition of 14-3-3 zeta protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3 zeta is involved in the regulation of protein kinase C (PKC) activity and 14-3-3 zeta binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3 zeta serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells. |
英文摘要 | The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3 zeta, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3 zeta interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3 zeta interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3 zeta interaction and mutation of Ser727 to Alanine abolished 14-3-3 zeta/Stat3 association. Inhibition of 14-3-3 zeta protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3 zeta is involved in the regulation of protein kinase C (PKC) activity and 14-3-3 zeta binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3 zeta serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells. |
WOS标题词 | Science & Technology |
类目[WOS] | Multidisciplinary Sciences |
研究领域[WOS] | Science & Technology - Other Topics |
关键词[WOS] | PROTEIN-KINASE-C ; PHOSPHORYLATION-DEPENDENT BINDING ; MM-PBSA METHOD ; IN-VIVO ; PROSTATE-CANCER ; PHOSPHATASE 2A ; APOPTOSIS ; RAF-1 ; 14-3-3-PROTEINS ; IDENTIFICATION |
收录类别 | SCI |
资助信息 | Chinese Academy of Sciences; Japan Society for the Promotion of Science |
语种 | 英语 |
WOS记录号 | WOS:000299771900018 |
公开日期 | 2012-04-01 |
源URL | [http://ir.ihb.ac.cn/handle/342005/16765] ![]() |
专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
作者单位 | 1.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China 2.Peking Univ, Ctr Theoret Biol, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China 3.Tokai Univ, Sch Sci & Technol, Tokyo 151, Japan |
推荐引用方式 GB/T 7714 | Zhang, Jia,Chen, Fangjin,Li, Wenliang,et al. 14-3-3 zeta Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells[J]. PLOS ONE,2012,7(1):e29554. |
APA | Zhang, Jia.,Chen, Fangjin.,Li, Wenliang.,Xiong, Qian.,Yang, Mingkun.,...&Ge, Feng.(2012).14-3-3 zeta Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells.PLOS ONE,7(1),e29554. |
MLA | Zhang, Jia,et al."14-3-3 zeta Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells".PLOS ONE 7.1(2012):e29554. |
入库方式: OAI收割
来源:水生生物研究所
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