时间：6月1日星期二15:30-17:00    

Time：3:30-5:00 PM，Tues.，June 1，2021

地点：西湖大学云栖校区5号楼1楼学术报告厅

Venue: Lecture Hall, 1F, Building 5, Yunqi Campus

主持人：西湖大学生命科学学院研究员 邹贻龙 

Host：Dr. Yilong Zou, School of Life Sciences

主讲嘉宾/Speaker:

Dr. Bao-Liang Song

Professor and Dean，College of Life Sciences，Wuhan University

Bao-Liang Song received a B.A. degree in Biology in 1997 from Nanjing University, China. He then entered a doctoral program at Shanghai Institute of Biochemistry and Cell Biology, China. He obtained his Ph.D. degree in 2002. From 2002 to 2005, Dr. Bao-Liang Song received his post-doctoral training in the laboratory of Drs. Joseph L. Goldstein and Michael S. Brown at UT Southwestern Medical Center, and worked with Dr. Russell DeBose-Boyd on the degradation of HMG-CoA reductase. He joined Shanghai Institute of Biochemistry and Cell Biology as Principle Investigator in 2005. He was appointed as Chief Scientist by the Ministry of Science and Technology of China in 2008, and won China National Funds for Distinguished Young Scientists in 2009. He won Tan KahKee Young Scientist Award in Life Sciences in 2012 and Arthur Kornberg Memorial Award in 2013.

讲座摘要/Abstract:

Cholesterol is an essential lipid and it costs lots of nutrients and energy to make such a molecule. Therefore, mammals increase cholesterol biosynthesis only after feeding and inhibit the process under fasting condition. However, the regulatory mechanisms of cholesterol biosynthesis at fasting-feeding transition are not fully understood. Here we show that the deubiquitylase USP20 stabilizes HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthetic pathway, at feeding state. The post-prandially increased insulin and glucose stimulate mTORC1 to phosphorylate USP20 at S132 and S134, which is further recruited to the HMGCR complex and antagonizes its degradation. The feeding-induced stabilization of HMGCR is abolished in the liver-specific Usp20 deficient mice and the Usp20-S132A/S134A knock-in mice. Genetic deletion or pharmacological inhibition of USP20 dramatically decreases diet-induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity as well as increases energy expenditure. These metabolic improvements by USP20 inhibition are reversed by the constitutively stable HMGCR(K248R). This study reveals an unexpected regulatory axis from mTORC1 to HMGCR through USP20 phosphorylation and demonstrates USP20 inhibitor as a potential cholesterol-lowering drug to treat metabolic diseases including hyperlipidemia, liver steatosis, obesity and diabetes. Dr.Song will also present their latest work about cholesterol transportation and modification on proteins.

联系人/Contact：

生命科学学院

于文越 yuwenyue@westlake.edu.cn