14-3-3ζ interacts with stat3 and regulates its constitutive activation in multiple myeloma cells14-3-3ζ与stat3在多发性骨髓瘤细胞和调节其本构激活.pdfVIP

14-3-3f Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells 1. 2. 3 1 1 1 1 Jia Zhang , Fangjin Chen , Wenliang Li , Qian Xiong , Mingkun Yang , Peng Zheng , Chongyang Li , 2 1 Jianfeng Pei *, Feng Ge * 1 Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China, 2 Center for Theoretical Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China, 3 School of Science and Technology, Tokai University, Tokyo, Japan Abstract 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- 3f, 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 14-3-3f interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3f interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3f interaction and mutation of Ser727 to Alanine abolished 14-3-3f/Stat3 association. Inhibition of 14-3-3f protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3f is involved in the regulation of protein kinase C (PKC) activity and 14-3-3f binding to Stat3 protects Ser727 dephosph