Unfolding Noncanonical Functions of Lysine Acetyltransferases

赖氨酸乙酰转移酶的非典型功能的揭示

• 批准号: 1808087
• 负责人: Y George Zheng
• 金额: $ 47.1万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808087&HistoricalAwards=false
• 关键词: Unfolding; Noncanonical; Functions; Lysine; Acetyltransferases

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Y. George Zheng from University of Georgia to investigate novel functions of enzymes called KATs. Previously the actions of KATs were known to control genes in an on-off fashion. Recent discoveries revealed new biological roles for KATs nearly every place in the cell, beyond the effect on genes. Functions of KATs are far more complex than previously regarded with impacts on multifaceted biological processes, including promoting entirely new chemical reactions. In this project, the PI designed a series of biochemical and cellular experimental studies to discover and characterize new functions of the major KAT enzymes. A highly multidisciplinary approach is proposed to dissect novel KAT functions. This pursuit is directly related to the PI's efforts in the training of graduate and undergraduate students in chemical biology and biochemistry. By undertaking these projects, students will learn how to apply advanced technologies to resolve key biological research problems. This project also integrates outreach activities to introduce high school students to the science of enzyme biochemistry. These research-related educational efforts are important to prepare next-generation scientists in chemical and biological sciences.The research project undertakes the development and application of new chemical biology tools to profile cellular substrates and new functions of the major KAT enzymes, with the goal of significantly advancing protein acylation research. The PI refines and applies a bioorthogonal labeling technology to investigate substrate profiles of the major KATs at the proteomic level. The PI and coworkers also investigate a novel lysine acylation mark in histones and non-histone proteins that they recently discovered. In these experiments, the team identifies enzymes that catalyze the addition and removal of the novel modification mark. The proposed research has great potential to generate new chemical tools for KAT activity investigation, offers a systematic view of KAT substrate distribution in the cell, provides a mechanistic understanding of KAT functions, and to a broader level, advances the knowledge of posttranslational modifications in chromatin remodeling, metabolic pathways, and signal transduction.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学部的生命过程化学项目正在资助Y博士。来自格鲁吉亚大学的乔治郑研究了一种叫做KAT的酶的新功能。 以前，已知KAT的作用是以开关方式控制基因。最近的发现揭示了KAT在细胞中几乎每个地方的新生物学作用，而不仅仅是对基因的影响。KAT的功能比以前认为的要复杂得多，对多方面的生物过程产生影响，包括促进全新的化学反应。 在该项目中，PI设计了一系列生化和细胞实验研究，以发现和表征主要KAT酶的新功能。一个高度多学科的方法，提出解剖新的KAT功能。这种追求直接关系到PI在培养研究生和本科生化学生物学和生物化学方面的努力。通过开展这些项目，学生将学习如何应用先进技术来解决关键的生物研究问题。该项目还整合了外展活动，向高中生介绍酶生物化学科学。这些与研究相关的教育工作对于培养化学和生物科学领域的下一代科学家非常重要。该研究项目致力于开发和应用新的化学生物学工具，以分析细胞基质和主要KAT酶的新功能，目标是显著推进蛋白质酰化研究。PI改进并应用生物正交标记技术在蛋白质组水平上研究主要KAT的底物谱。PI及其同事还研究了他们最近发现的组蛋白和非组蛋白蛋白中的一种新的赖氨酸酰化标记。在这些实验中，研究小组确定了催化添加和去除新修饰标记的酶。拟议的研究具有很大的潜力，为KAT活性研究产生新的化学工具，提供了细胞中KAT底物分布的系统视图，提供了对KAT功能的机制理解，并在更广泛的水平上，推进了染色质重塑，代谢途径，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Identification and Profiling of Histone Acetyltransferase Substrates by Bioorthogonal Labeling

通过生物正交标记鉴定和分析组蛋白乙酰转移酶底物

• DOI: 10.1002/cpz1.497
• 发表时间: 2022
• 期刊: Current Protocols
• 作者: Song, Jiabao;Han, Zhen;Zheng, Y. George
• 通讯作者: Zheng, Y. George

Identification of lysine isobutyrylation as a new histone modification mark.

• DOI: 10.1093/nar/gkaa1176
• 发表时间: 2021-01-11
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Zhu Z;Han Z;Halabelian L;Yang X;Ding J;Zhang N;Ngo L;Song J;Zeng H;He M;Zhao Y;Arrowsmith CH;Luo M;Bartlett MG;Zheng YG
• 通讯作者: Zheng YG