报告题目: BRD4 in Gene-Specific Targeting and Cancer Therapy

报告人: Cheng-Ming Chiang教授（University of Texas Southwestern Medical Center）

主持人: 翁杰敏 教授

开始时间: 2016-5-16  13:30-14:30 （周一下午）

报告地址: 闵行校区天美娱乐534报告厅

主办单位: 天美娱乐 科技处

 

报告人简介:Cheng-Ming Chiang, Professor of Simmons Comprehensive Cancer Center and Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center at Dallas. He was graduated from National Taiwan University. He got his doctor’s degree from University of Rochester. Later he became a postdoctoral in University of Rochester and Rockefeller University. He was trained as a biochemist and molecular virologist specializing in mechanistic studies of transcription, chromatin, gene regulation, and post-translational modification using viral and cellular systems. His contributions to science include Development of FLAG Epitope Tagging Technology for Protein Complex Purification; In Vitro Reconstitution of the General Transcription Machinery; Mechanistic Studies of HPV Chromatin-Dependent Transcription and Gene Regulation; Covalent Modification-Regulated p53 Function in Normal and Cancer Cells; Elucidation of BRD4 Function in Gene-Specific Targeting and Cancer Therapeutics.

 

报告简介⚠🤸🏿‍♂️：Bromodomain-containing protein 4 (BRD4) is an epigenetic reader protein recognizing acetyl-lysine in histones and nonhistone proteins via its N-terminal tandem bromodomains.  Although BRD4 is a universal chromatin-binding factor, functional inactivation of BRD4 surprisingly shows select effects on target gene transcription.  Emerging data also implicate BRD4 in diverse cellular processes including cell cycle progression, DNA damage response, chromatin structure maintenance, stem cell reprogramming, viral latency and reactivation, and cancer development and therapeutics.  These multifunctional effects of BRD4 are regulated in part by casein kinase II (CK2)-mediated phosphorylation and protein phosphatase 2A (PP2A)-mediated dephosphorylation that in turn modulate BRD4 interaction with different cellular and viral proteins.  Phosphorylation-regulated BRD4 function dictates G9a lysine methyltransferase activity in methylating histone H3 and p53 tumor suppressor as well as functional recruitment of human papillomavirus (HPV) E2 transcription/replication factor to targeted HPV and cellular gene promoters.  The molecular switch controlled by cancer cell-addicted CK2 activity highlights the elegance of phosphorylation-regulated intra- and inter-molecular contact switches in modulating BRD4 function in gene-specific targeting and pathway selectivity.  A new class of small compounds targeting this phospho region of BRD4 provides a more select inhibition of gene transcription compared to the widely used JQ1- and I-BET-derived bromodomain inhibitors.