报告题目：Orphan Nuclear Receptor TR3 Acts in Autophagic Cell Death via Mitochondrial Signaling Pathway
报告人：吴乔 教授
主持人：叶升 教授
时 间：2013年10月24日（周四）下午4点
地 点：医学院综合楼205报告厅
主持人：叶升 教授
时 间：2013年10月24日（周四）下午4点
地 点：医学院综合楼205报告厅
报告人简介：
厦门大学生命科学学院二级教授，博士生导师，国家杰出青年科学基金获得者，福建省闽江学者特聘教授，细胞应激生物学国家重点实验室副主任。
1990年获厦门大学理学硕士学位；中美联合培养博士研究生，1996年获厦门大学理学博士学位。毕业后留校任教。目前主要研究领域为核受体蛋白相互作用和蛋白修饰、核受体参与细胞凋亡/自噬诱导的作用机理及其信号转导调控等基础理论研究，以及抗肿瘤药物、糖脂代谢药物的分子机制、药物靶点和药物筛选模型建立等应用基础研究。主持国家和省部级基金20多项，包括国家杰出青年科学基金、国家基金重点项目和国际重大合作项目、973课题等。以通讯作者身份在国际权威刊物如Nature Chemical Biology、The EMBO Journal、EMBO Molecular Medicine、Gut、Cancer Research等发表论文40余篇。研究成果获福建省自然科学奖一等奖。先后培养博士生和硕士生20多名。获"卢嘉锡优秀导师奖"和 "药明康德生命化学研究奖-杰出成就奖"等荣誉称号。
讲座摘要：
Melanoma is the most aggressive form of skin cancer with notorious resistance to apoptosis, which is a major barrier to the successful melanoma treatment. It is of great importance to identify alternative therapeutic strategies to treat melanoma other than resorting to the apoptotic induction. Autophagy, a process known to provide a survival advantage to cells during nutrient deprivation or other stresses, has also been linked to cell death, yet the associated mechanisms are largely undercharacterized. Herein it is discovered that melanoma can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to the cellular demise is launched by a specific chemical compound 1-(3,4,5-trihydroxyphenyl)- nonan-1-one (THPN), newly acquired from screening an in house library of TR3-targeting compounds. The autophagic cascade is comprised of TR3 translocation to mitochondria by interacting with the mitochondrial outer membrane protein Nix, crossing into mitochondrial inner membrane through Tom40/Tom70 channel proteins; dissipation of mitochondrial membrane potential by a permeability transition pore complex ANT1/VDAC1, and induction of autophagy. This autophagic process leads to excessive mitochondria clearance and irreversible cell death. It implicates a novel approach to melanoma therapy by activating a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.
