FASEB's The Reversible Protein Acetylation in Health and Disease Conference

摘要 在过去的几年里，基因组的“表观遗传”调节变得越来越重要， 了解衰老和年龄相关疾病的病因和基本机制。关键 表观遗传调节是两类赖氨酸修饰酶，组蛋白脱乙酰酶（sirtuins和 HDAC）和组蛋白乙酰转移酶（HAT），也分别称为擦除器和写入器。乙酰基 赖氨酸中和相对于裸赖氨酸侧链的阳离子电荷，并且还产生吸引性表面 用于结合含有溴结构域的蛋白，也称为阅读蛋白。这些乙酰基-赖氨酸书写者， 橡皮擦和阅读器对于维持正常的表达模式、细胞周期进程、DNA 修复、干细胞、线粒体、细胞命运和分化。这些乙酰赖氨酸功能的改变 相关蛋白质与基因表达的表观遗传沉默有关， 基因，导致癌细胞增殖。此外，乙酰赖氨酸途径的变化被认为是 导致多种其他疾病和衰老机制。几种广谱HDAC抑制剂 已经被FDA批准用于治疗各种癌症。它们精确的分子机制 癌症和影响其他生物医学过程仍然难以捉摸。靶向HAT和HDAC用于治疗 目的一直是一个非常感兴趣和成功的领域，并取得了令人兴奋的新进展， 近年来在癌症和其他疾病中靶向阅读器和乙酰化赖氨酸之间的相互作用。作为 唯一的会议致力于蛋白质乙酰化，这个一年两次的会议发挥了重要作用， 40多位世界领导人和约120名与会者。一个主要目标是转移知识， 促进基础学术研究人员、临床科学家和工业研究人员之间的合作， 了解赖氨酸乙酰化如何控制人类健康以及如何预防和治疗各种癌症 与年龄有关的疾病。第二个目标是促进年轻人的发展和兴趣， 调查人员帮助支持他们的职业发展。与会者在会场住宿和用餐， 他们有充足的时间进行非正式的集思广益和建立联系。有16个计划中的会谈， 从提交的摘要和海报奖获奖者中选出的科学家，这对他们的职业生涯很重要 发展我们还将举行关于专业发展和职业选择的小组讨论，旨在 为年轻的研究人员提供更多支持。此外，还将举行多样性网络会议， 多个会议将在会议上强调的演讲者会议。这次会议开得特别及时 因为乙酰化、代谢和癌症之间存在联系。此外，令人兴奋的新基础 不断有新的发现被报道，例如发现新的赖氨酸翻译后修饰 (e.g. 3-羟基丁酰赖氨酸和棕榈酰赖氨酸），其可以通过沉默调节蛋白或HDAC去除，并且 发现这些修饰可以调节转录、细胞信号传导和蛋白质分泌。因此，我们认为， 要求支持第八届FASEB关于健康中可逆蛋白质乙酰化的半年期会议， 疾病将于2021年8月9日至14日在波多黎各多拉多举行。

Abstract Over the past few years, the “epigenetic” regulation of the genome has become increasingly important to understanding both the etiology and fundamental mechanisms of aging and age-related diseases. Key to epigenetic regulation are two classes of lysine-modifying enzymes, the histone deacetylases (sirtuins and HDACs) and the histone acetyltransferases (HATs), also known as erasers and writers, respectively. Acetyl- lysine neutralizes the cationic charge relative to the naked Lys sidechain and also creates an attractive surface for binding to proteins containing bromodomains, also known as reader proteins. These acetyl-Lys writers, erasers, and readers are critical for maintaining normal expression patterns, cell cycle progression, DNA repair, stem cells, mitochondria, cell fate, and differentiation. Alterations in the functions of these acetyl-Lys related proteins have been linked to epigenetic silencing of gene expression including tumor suppressor genes, leading to cancer cell proliferation. Moreover, changes in acetyl-Lys pathways are believed to contribute to a variety of other diseases and aging mechanisms. Several broad spectrum HDAC inhibitors have been approved by FDA to treat various cancers. Their precise molecular mechanisms in controlling cancer and influencing other biomedical processes remain elusive. Targeting HATs and HDACs for therapeutic purposes has been an area of great interest and success, and exciting new progress has also been made in recent years in targeting interactions between readers and acetylated lysines in cancer and other diseases. As the only conference dedicated to protein acetylation, this biannual meeting plays an essential role in bringing together more than 40 world leaders and ~120 participants. A primary objective is to transfer knowledge and foster collaboration between basic academic researchers, clinical scientists, and industrial researchers to understand how lysine acetylation controls human health and how to prevent and treat a diverse set of cancers and age-related diseases. A second objective is to foster the development and interests of younger investigators to help support their career development. The participants stay and eat at the meeting venue so they have ample time to for informal brainstorming and networking. There are 16 planned talks from junior scientists selected from the submitted abstracts and poster prize winners, which is important for their career development. We will also have a panel discussion on professional development and career options, aimed to provide further support for the young investigators. Moreover, there will be a diversity networking session, and multiple meet the speaker sessions that will be highlighted at the meeting. This meeting is particularly timely because of a linkage of acetylation, metabolism, and cancer. Furthermore, exciting new fundamental discoveries are continuing to be reported, such as the discovery of new lysine post-translational modifications (e.g. 3-hydroxybutyryl lysine and palmitoyl lysine) that can be removed by sirtuins or HDACs, and the discovery that these modifications can regulate transcription, cell signaling, and protein secretion. Therefore, support is requested for the 8th biannual FASEB conference on reversible protein acetylation in health and disease to be held in Dorado, Puerto Rico on August 9-14, 2021.