Proteostasis regulation through the early secretory pathway
报告人：马文福 斯隆凯特林纪念癌症研究中心，纽约，研究助理
报告时间：2018年4月19日（周四）12:30-14:00
报告地点：8797威尼斯老品牌东十一楼221会议室
报告人简介：
教育背景：
复旦大学, 上海， 2006.9 – 2011.1 博士学位 疾病蛋白质组学 导师 张明杰院士
复旦大学, 上海 2003.9 – 2006.7 硕士 化学导师 王文宁教授
华东理工大学, 上海 1999.9 – 2003.7 学士 化学
科研经历：
斯隆凯特林纪念癌症研究中心, 纽约 2016.5 – 至今 研究助理 ER 蛋白质质量控制
霍华德休斯医学研究院, 纽约 2011.3 – 2016.5 博士后 COPI, COPII 底物识别分子机制
发表文章：
• Ma Wenfu, Goldberg Elena and Goldberg Jonathan. ER retention is imposed by COPII protein sorting and is attenuated by 4-Phenylbutyrate. Elife 2017;Jun 8;6:e26624
• Ma Wenfu and Goldberg Jonathan. The TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats. Proceedings of the National Academy of Sciences, 2016 Sep 6; 113(36)
• Ma Wenfu and Goldberg Jonathan. Rules for the recognition of dilysine retrieval motifs by coatomer. EMBO J. 2013 Apr 3;32(7):926-37
• Ma Wenfu, Yuan Shang, Zhiyi Wei, Wenyu Wen, Wenning Wang and Mingjie Zhang. Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the Kinase. Structure 2010, 18,1502-1511
• Yuanyuan Xie, Zhen Cao, Wai Pung E. Wong, Youxin Guan, Wenfu Ma, Jenny Q. Zhang, Edward G. Walczak, Devan Murphy, Leili Ran, Inna Sirota, Shangqian Wang, Shipra Shukla, Dong Gao, Simon R.V. Knott, Kenneth Chang, John Wongvipat, Cristina R. Antonescu, Gregory Hannon, Ping Chi*, Yu Chen* COP1-ETS axis regulates ERK transcriptional output and modulates sensitivity to MAPK inhibitors. Jour-nal of Clinical Investigation J Clin Invest. 2018 Jan 23.
• Wenfu Ma*, GoldbergElena*andGoldbergJonathan. Misfolded protein elimination through the coupling of COPII trafficking and the post-ER quality control machinery. (In submission) * Co-first author
美国专利
• Ma Wenfu, Goldberg Elena and Goldberg Jonathan. Methods for modifying Endoplasmic Reticulum pro-cessing of protein. Atty. Dkt. No:115872-0173
Abstract
Protein misfolding and the unfolded protein response (UPR) are associated with numerous human diseases including neuronal degeneration, diabetes and cancer. Only native protein cargo can exit ER in COPII vesicles, whereas the misfolded proteins are largely excluded out of vesicles. We investigate the protein ER retention mechanism using an FDA-approved drug called 4-phenylbutyrate (4-PBA), which we show targets COPII Sec24. 4-PBA can restore the misfolded protein trafficking and release ER stress through competition with COPII canonical cargoes. For the first time, the trafficking machineries can be drugable. Another case of ER retention is that protein with a dilysine motif can be retrograde transported back to ER through COPI vesicles. I will delineate the rules for COPI cargo recognition. The last example of ER retention is how COPII package macromolecule procollagen through its adaptor Tango1/cTAGE5. During the assembly of COPII coat on vesicles, the adaptors are being forced to the budding neck on ER using a unique retention strategy. Meanwhile, the Tango1/cTAGE5 facilitates the COPII vesicle to grow into a mega carrier by polymerizing the inner coat.
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