苏州大学药学院欢迎您!

[12-16]Targeting Oncogenic MYC for Cancer Treatment

发布者:彭蓓发布时间:2019-12-12浏览次数:185

报告题目:Targeting Oncogenic MYC for Cancer Treatment

报 告 人:魏永 博士(加拿大多伦多大学)

报告时间:20191216日(星期一)上午9:00

报告地点:独墅湖校区二期云轩楼2301会议室室

  

报告人简介:

Dr. Yong Wei completed his Ph.D. at University of Science and Technology of China under the supervision of Dr. Yuhui Dong. After graduation in Dec 2013, Dr. Wei moved to University of Toronto and pursued his postdoctoral training with Dr. Gil Prive in Canada. Given his highly interest in cancer research and strong background in protein science, he moved to Linda Penn's group for his second postdoc training to investigate the molecular basis and potential therapeutic advantages of oncogenic MYC protein. Identification and understanding of novel protein interactions with MYC would facilitate the discovery of new biological models and therapeutic targets for clinical innervation. Toward this goal, Dr. Wei has established the precision MYC-proteins interaction maps and elucidated the biological function of the specific identified interactions in the context of cancer cells. Such information is crucial to understanding cellular pathway and developing effective therapies for the treatment of cancer with highly expressed MYC. In addition, Dr. Wei has developed a high-throughput screening platform for cancer drug discovery by directly targeting MYC and its interactors. Dr. Wei’s work presents a guide to explore the MYC-interactors network to facilitate cancer biology.


报告摘要:

Transcription factor c-MYC is a potent oncoprotein, however the mechanism of transcriptional regulation via MYC:protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediatingMYC:TBP interactions using structural, biochemical and cellular approaches. A 2.4Å resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1(TAF1TAND1). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independent ofTAF1TAND1. Modelling reveals this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC:TBP interaction compromise MYC activity. We propose that MYC:TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly. Using the same pipeline, we have identified couples of other interactors with important biological functions andthe feasibility of targeting MYC for cancer treatment.