医学院科技活动月暨杏林讲坛(30)

资讯来源:新葡的京集团网址发布时间:2022-05-25点击量:10

题目:Ubiquitin-mediated Regulation of Autophagy and ER Morphology

报告人:刘艳芬  教授

时间:2022年5月27日(周晚上19:00-20:30

线上腾讯会议ID:917-690-669

 

讲座简介

   Ubiquitination is an important type of protein posttranslational modification and plays a crucial role in various pathways. In an attempt to understand the ubiquitin-mediated autophagy regulation, we screened the ubiquitin enzymes functioning in autophagy. Through an unbiased screen strategy, we identified an E3 ubiquitin ligase complex, Linear Ubiquitin Chain Assembly Complex (LUBAC), and a de-ubiquitinating enzyme (DUB) OTULIN both localize to phagophore to control autophagy initiation and maturation. Knockdown of the LUBAC key component RNF31/HOIP inhibits autophagy initiation, and cells are more sensitive to bacterial infection. By contrast, OTULIN knockdown promotes autophagy initiation yet blocks autophagy at a premature stage. Our study thus demonstrates that linear ubiquitination regulates autophagy initiation and maturation to protect the host cell against pathogenic infection.  In a parallel study, we identified an ER-localized E3 ligase SYVN1 participates in ER remodeling by ubiquitin modification of the ER shaping proteins Atlastins (ATLs). Defect of ATLs leads to abnormal ER structure and hereditary spastic paraplegia (HSP), a neurodegenerative disease with progressive spasticity. Ubiquitination of ATL1 by SYVN1 does not lead to protein degradation but inhibits the GTPase activity of ATL1. Overexpression of atln-1 (ATL1 orthologue) in the Caenorhabditis elegans motor neurons leads to abnormal distribution of the ER network in axon, which is rescued by the co-expression of sel-11 (SYVN1 orthologue). Therefore, our studies provide evidence that protein ubiquitination regulates different processes in a highly specific mode.

报告人简历:

刘艳芬,博士生导师,上海科技大学生命科学与技术学院PI。博士毕业于北京协和医学院/北京生命科学研究所 (NIBS),2009年到2015年,在美国NIH从事博士后研究。主要研究方向为蛋白质质量控制与人类疾病研究,包括蛋白质质量控制在人类退行性疾病(如帕金森症)发生发展过程中的作用机制,自噬小体的膜起源机制以及泛素依赖的细胞自噬的机制以及包括内质网、线粒体、RNA 应激复合物在内的细胞器降解机理。在Autophagy,molecular cell,elife,JBC,等高水平期刊发表论文12篇。主持国家自然科学基金3项。