报告题目：“Avian reovirus p17 protein functions as a nucleoporin Tpr suppressor that positively regulates p53, PTEN and p21 and negatively regulates PI3K-Akt-mTOR and ERK pathways enhancing virus replication”

　　报 告 人：刘宏仁 博士、教授（台湾中兴大学分子生物学研究所所长，生命科学院荣誉特聘教授　）

　　报告时间：2013年9月4日（星期三）下午3:00-5:00

　　报告地点：动物医学院二楼会议室

　　报告内容：主要阐述禽里奥病毒非结构蛋白p17调节病毒复制的分子机制及细胞信号通路。

　　报告人简介：刘宏仁 荣誉特聘教授兼所长

　　刘宏仁教授 1996-1997在加拿大Manitoba大学医学院做博士后研究员，1997-2010历任台湾屏东科技大学兽医学系助理教授、副教授、教授，2006-2010担任屏东科技大学生物科技研究所所长。2010-迄今，任中兴大学分子生物学研究所特聘教授，2013年7月担任中兴大学分子生物学研究所所长。2011-迄今，担任Open Journal of Veterinary Medicine， J. of Contemporary Virology的主编（Editor-in Chief）,9个国际期刊的编委（editorial board），刘宏仁教授领导的团队在Journal of  Virology, Journal of Biological Chemistry, Veterinary Microbiology等国际重要学术期刊发表学术论文150多篇，在病毒讯息传递的分子细胞机制研究、病毒蛋白生物功能和疫苗研发等方面取得了显著成绩。最近他的团队在avian reovirus (ARV) p17 蛋白功能方面取得重大突破，相应成果撰写的论文已被Journal of Biological Chemistry接收，本次报告他将对这一最新成果做详细介绍。

　　欢迎广大师生积极参加！

　　　　　　　　　　　　动医学院
　　　　　　　　　　　　2013年8月28日

　　Abstract

　　The p17 protein of avian reovirus (ARV) has been shown to regulate cellular translation, cell cycle, and autophagy;nevertheless, the involved cellular factors and upstream signaling pathways remain largely unknown. Here, we demonstrate for the first time that p17 is functions as Tpr suppressor negatively regulating nucleoporin Tpr by interaction with Tpr and by downregulation of Tpr gene expression. We defined that the nuclear localization signal (NLS) of p17 is required for Tpr binding. Suppression of Tpr by p17leads p53 and p21 nuclear accumulation, thereby positively regulating PTEN and negatively regulating pI3K/Akt/mTOR pathway, ERK, and CDKs. In this work, we uncovered that p17 stablizes PTEN by enhancing PTEN phosphorylation and by elevating the binding of Rak and β-arrestin to PTEN to prevent it from E3 ligase NEDD4-1 targeting. Furthermore, p17 activates PTEN by promoting translocation from cytoplasm to membrane through a Rock-1/β-arrestin-dependent pathway. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated inhibition of cyclin D1-CDK4 and cyclin E-CDK2, which results in cell cycle arrest. In addition to downregulation of Akt through activation of PTEN, p17 also deregulated mTORC2 by disrupting mTORC2 assembly and by reducing mTORC2-ribosome association via ubiquitin-mediated MDM2-ribosomal proteasomal degradation pathway. Furthermore, p17 is also capable of disrupting mTORC1 assembly by enhancing the binding of PRAS40 to raptor and FKBP38 to mTORC1 leading to inhibition of phosphorylation of p70S6K1 and 4E-BP1, thereby causing cellular translation shutoff. Downregulation of Tpr and upregulation of p53, PTEN, p21, by p17 lead to inactivation of PI3K/Akt/mTORC1 and ERK pathway benefiting virus replication.