文献类型：期刊文献

英文题名：Elucidating respective functions of two domains BIR and C-helix of human IAP survivin for precise targeted regulating mitotic cycle, apoptosis and autophagy of cancer cells

作者：Hu, Fabiao[1,2];Pan, Daxia[1,2];Zheng, Wenyun[3,4];Yan, Ting[1,2];He, Xiujuan[3,4];Ren, Fuzheng[3,4];Lu, Yiming[5];Ma, Xingyuan[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[5]Second Mil Med Univ, Sch Pharm, Dept Biochem Pharm, Shanghai 200433, Peoples R China

年份：2017

卷号：8

期号：69

起止页码：113687

外文期刊名：ONCOTARGET

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000419570400029)】；

基金：This work was supported by the National Natural Science Foundation (31670944, 81673345), Science and technology innovation action plan of Shanghai (14431904300, 17431904600), Shanghai Pujiang Program (13PJD012), and supported by the National Science Research Project "Significant New Drugs Created" of Eleventh Five-year Plan (2009ZX09103-693).

语种：英文

外文关键词：BIR and CC domains; survivin; cell cycle; apoptosis and autophagy; breast cancer cells

摘要：Survivin was the smallest member of the IAP family, which was over expressed in many different cancers, and considered to be a promising hot target for cancer therapy, and our previous study demonstrated that multiple dominant negative mutants from full-length survivin could have many complex effects on cancer cells, such as cell cycle, apoptosis, and autophagy. But it was not yet known what role the two main domains played in those functions, which would be very important for the design of targeted anticancer drugs and for the interpretation of their molecular mechanisms. In this study, based on preparation the two parts (BIR domain and CC domain) of survivin by genetic engineering and cell characterization assay, we discovered that BIR (T34A)-domain peptide could inhibit Bcap-37 cells growth in a dose-and time-dependent manner, increase the proportion of G2/M phase, and induce caspase-dependent apoptosis via the mitochondrial pathway. While CC (T117A)-domain peptide increased the proportion of S-phase cells and increased the level of the autophagy marker protein LC3B significantly. These further experiments confirmed that TAT-BIR (T34A) peptide could be used to inhibit cell proliferation, promote apoptosis, and block mitosis, and TAT-CC (T117A) peptide showed mainly to promote autophagy, process of DNA replication, and mitosis to breast cancer cells. This research will lay the foundation for interpreting the multifunction mechanism of survivin in cell fates, further make senses in developing the anticancer drugs targeting it precisely and efficiently.