FASEB SRC on Reversible Acetylation in Health and Disease

FASEB SRC 关于健康和疾病中的可逆乙酰化

• 批准号: 9750429
• 负责人: PHILIP A COLE
• 金额: $ 0.85万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750429
• 关键词: Acetylation; Acetyltransferase; Aging; American; Antineoplastic Agents; Architecture; Area; Basic Science; Binding; Binding Proteins; Biochemistry; Biological; Biology; Bromodomain; Carbon; Cations; Cell Cycle Progression; Cell Proliferation; Cell physiology; Cells; Cellular biology; Charge; Chemicals; Chemoprevention; Clinical; Collaborations; Communities; Country; DNA Repair; DNA biosynthesis; Deacetylase; Development; Dietary Intervention; Disease; Docking; Drug Targeting; EP300 gene; Eating; Educational workshop; Enzymes; Epigenetic Process; Etiology; European; FDA approved; Faculty; Female; Fertilization; Fostering; Gene Expression; Gene Silencing; Genetic; Genetic Transcription; Genome; Genome Stability; Germany; Goals; Growth; Health; Histone Deacetylase; Histone Deacetylase Inhibitor; Homeostasis; Human; Image; Immune response; Industrialization; Industry; International; Investigation; Italy; Knowledge; Link; London; Longevity; Lysine; Malignant Neoplasms; Mass Spectrum Analysis; Metabolic Diseases; Metabolism; Methods; Methylation; Mitochondria; Modification; Molecular; Molecular Biology; Molecular Mechanisms of Action; Montana; New Agents; Nuclear; Oral; Participant; Pathway interactions; Pattern; Pharmacology; Phosphorylation; Play; Portugal; Post-Translational Protein Processing; Process; Protein Acetylation; Protein Secretion; Proteins; Public Health; Reader; Regulation; Reporting; Research; Research Personnel; Role; Scientist; Series; Side; Signal Transduction; Sirtuins; Site; Stem cells; Structure; Surface; Talents; Technology; Testing; Therapeutic; Time; Training; Tumor Suppressor Genes; Underrepresented Minority; age related; base; cancer cell; career; career development; drug discovery; epigenetic regulation; epigenome; graduate student; histone acetyltransferase; human disease; improved; inhibitor/antagonist; innovation; insight; interest; meetings; novel; novel therapeutic intervention; novel therapeutics; overexpression; palmitoylation; posters; prevent; protein function; summer research; symposium

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. Although targeting HATs for therapeutic purposes has been relatively slow compared to targeting deacetylases, exciting new progress has also been made in recent years, including the recent discovery of A- 485 as a p300/CBP inhibitor. In addition, targeting bromodomains in cancer is a very active area. 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, 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 series of ask the experts discussion sections over lunch that will allow attendees to gain insight into specialized technologies (mass spectrometry, structural approaches, chemical biology methods, imaging strategies) 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 7th biannual FASEB conference on reversible protein acetylation in health and disease to be held in Lisbon, Portugal August 4 -9, 2019.

摘要 在过去的几年里，基因组的“表观遗传”调控对于理解 衰老和与年龄相关的疾病的病因和基本机制。表观遗传调控的关键有两点 赖氨酸修饰酶、组蛋白去乙酰化酶（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。乙酰赖氨酸中和了相对于裸 赖氨酸侧链，也产生了一个有吸引力的表面，用于结合含有溴结构域的蛋白质，也称为溴结构域。 阅读器蛋白。这些乙酰基-赖氨酸写入器、擦除器和读取器对于维持正常表达模式至关重要， 细胞周期进程、DNA修复、干细胞、线粒体、细胞命运和分化。职能的改变 这些乙酰-赖氨酸相关蛋白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有助于 各种其他疾病和衰老机制。几种广谱HDAC抑制剂已被FDA批准 来治疗各种癌症它们在控制癌症和影响其他生物医学方面的精确分子机制 进程仍然难以捉摸。尽管与治疗目的相比，靶向HAT相对缓慢， 针对脱乙酰酶，近年来也取得了令人兴奋的新进展，包括最近发现的A- 485作为p300/CBP抑制剂。此外，靶向癌症中的溴结构域是一个非常活跃的领域。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在汇集40多个世界上重要的作用。 领导和120名参与者。一个主要目标是转移知识和促进基本 学术研究人员，临床科学家和工业研究人员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和与年龄有关的疾病。第二个目标是促进 青年调查员的发展和兴趣，以帮助支持他们的职业发展。参与者留下来， 在会议地点用餐，这样他们就有足够的时间进行非正式的头脑风暴和建立联系。计划有16个 从提交的摘要中选出的年轻科学家的演讲，这对他们的职业发展很重要。我们将 还将举行一次关于专业发展和职业选择的小组讨论， 年轻的调查员此外，午餐期间将有一系列的专家讨论部分， 与会者将深入了解专业技术（质谱、结构方法、化学生物学 方法，成像策略），将在会议上强调。这次会议特别及时，因为 乙酰化、代谢和癌症的联系。此外，令人兴奋的新的基本发现正在继续 报道，例如发现新的赖氨酸翻译后修饰（例如3-羟基丁酰赖氨酸和棕榈酰赖氨酸）。 赖氨酸），以及发现这些修饰可以调节转录， 细胞信号和蛋白质分泌。因此，要求支持第七届FASEB半年度可逆 健康和疾病中的蛋白质乙酰化将于2019年8月4日至9日在葡萄牙里斯本举行。