生命科学联合中心
学术报告
Title：A Family of Metabolism-sensitive Lysine Acylation Pathways: Biochemistry, epigenetics and pathophysiology
Speaker： Yingming Zhao, Ph.D.
Ben May Department for Cancer Research
The University of Chicago
Time：2018-3-29（周四），13:00 -14:00 pm
Venue：邓佑才报告厅，北京大学金光生命科学大楼
Host：王初，北大-清华生命科学联合中心
Abstract：
The protein post-translational modifications (PTMs) and their regulatory enzymes play a crucial role in diverse biological processes. Dysregulation of the PTM pathways can lead to diseases, such as cancer. Unfortunately, it remains unknown if additional PTM pathways exist. In addition, many of the PTM-regulatory enzymes were incorrectly annotated and their enzymatic substrates were poorly characterized, thus hindering our understanding of their biological functions. In this talk, we will present our discovery of nine types of new short-chain, lysine acylation pathways: propionylation, butyrylation, crotonylation, malonylation, succinylation, glutarylation, 2-hydroxyisobutyrylation, 3-hydroxybutyrylation, and benzoylation. We identified about ~500 new histone marks, which more than doubles the number of previously described histone marks that were discovered over the past few decades. We developed a powerful proteomics approach for identifying diverse binding proteins for the histone marks. Some of the new histone marks are associated with chromatin structure and transcriptional activity, which are different from the well-studied histone lysine acetylation, suggesting their unique roles in epigenetic mechanism. These pathways contribute to cellular dysfunctions associated with multiple inborn metabolic diseases, therefore offering new avenues for therapeutic intervention. The data lays a foundation for studying biological functions of these PTM pathways. Our results will have a wide implication for PTM-enzyme-based drug discovery, including defining biological functions of a druggable enzyme, developing a relevant assay for drug screening, and identifying biomarkers.
