Histone Deacetylases and reversible acetylation in signaling and disease

描述（由申请人提供）：通过共价修饰（如磷酸化）调节蛋白质功能是许多生物过程的基础。在过去的几年里，新出现的证据表明，蛋白质赖氨酸残基的乙酰化可能与可逆磷酸化一样是细胞通路的主要调节机制。组蛋白乙酰化是可逆乙酰化如何控制染色质结构和功能的经典例子，允许适当水平的基因表达。然而，现在已经确定bbbb100非组蛋白可能受到这种修饰的急性调节。随着组蛋白乙酰转移酶（hat）和去乙酰化酶（hdac）酶的首次克隆（约10年前），该领域的研究出现了爆炸式增长。本次FASEB会议将主要关注HDACs的生物学和机制。将特别强调这些酶在与年龄相关疾病（如神经退行性疾病、阿尔茨海默病和帕金森病、记忆丧失、糖尿病和癌症）相关的途径中的功能。除了提供HDACs在基因调控中所起作用的分子理解外，还将重点关注非组蛋白的乙酰化及其对中枢代谢途径的影响。特别是，关键主题将包括sirtuins去乙酰化酶，这是参与衰老和代谢的nadd依赖性去乙酰化酶。本次会议提案要求支持12位目前处于职业生涯早期阶段的科学家出席和参与。用于此目的的资金将为早期职业科学家提供极好的培训机会，他们将展示他们的工作并了解这一新兴领域的最新发展。共价修饰对细胞蛋白的调控是许多生物过程的基础。在过去的几年里，新出现的证据表明，蛋白质的乙酰化控制着细胞功能的执行能力。2009年FASEB夏季会议“信号和疾病中的组蛋白去乙酰化和可逆乙酰化”将主要关注去除这种修饰的酶的生物学途径和机制，即组蛋白去乙酰化酶，或hdac。将特别强调这些酶在与年龄相关疾病（如神经退行性疾病、阿尔茨海默病和帕金森病、记忆丧失、糖尿病和癌症）相关的途径中的功能。除了提供HDACs在基因调控中所起作用的分子理解外，还将重点关注这些酶如何影响中枢代谢途径。特别是，关键主题将包括sirtuins去乙酰化酶，这是代谢相关的去乙酰化酶，参与衰老和代谢调节。本次会议提案要求支持12位目前处于职业生涯早期阶段的科学家出席和参与。用于此目的的资金将为早期职业科学家提供极好的培训机会，他们将展示他们的工作并了解这一新兴领域的最新发展。

DESCRIPTION (provided by applicant): Regulation of protein function by covalent modifications, such as phosphorylation, is fundamental to many biological processes. Over the last several years, emerging evidence suggests that acetylation of protein lysine residues may rival reversible phosphorylation as a major regulatory mechanism of cellular pathways. Histone acetylation is a classical example of how reversible acetylation controls the structure and function of chromatin, permitting the appropriate level of gene expression. However, it is now established that >100 non-histone proteins might be acutely regulated by this modification. With the first cloning (~10 years ago) of histone acetyltransferase (HATs) and deacetylase (HDACs) enzymes, there has been an explosion of research in the field. This FASEB conference will focus primarily on the biology and mechanism of the HDACs. There will be particular emphasis on the function of these enzymes in pathways that are associated with age-related diseases, such as neurodegenerative disorders, Alzheimer's and Parkinson's disease, memory loss, diabetes and cancer. In addition to providing a molecular understanding of the roles played by HDACs in gene regulation, there will be an important emphasis on acetylation of non-histone proteins and the impact to central metabolic pathways. Particularly, key topics will include the sirtuins deacetylases, which are NAD-dependent deacetylases involved in aging and metabolism. This conference proposal requests support for attendance and participation by 12 scientists who are currently at the early stages of their careers. Use of funds for this purpose will provide an excellent training opportunity for early-career scientists who will present their work and learn about the latest developments in this burgeoning field. Regulation of cellular proteins by covalent modifications is fundamental to many biological processes. Over the last several years, emerging evidence suggests that acetylation of proteins controls the ability to perform their cellular functions. This 2009 FASEB summer conference "Histone deacetylases and reversible acetylation in signaling and disease" will focus primarily on the biological pathways and mechanisms of the enzymes that remove this modification, namely the histone deacetylases, or HDACs. There will be particular emphasis on the function of these enzymes in pathways that are associated with age-related diseases, such as neurodegenerative disorders, Alzheimer's and Parkinson's disease, memory loss, diabetes and cancer. In addition to providing a molecular understanding of the roles played by HDACs in gene regulation, there will be an important emphasis on how the enzymes impact central metabolic pathways. Particularly, key topics will include the sirtuins deacetylases, which are metabolically-link deacetylases involved in aging and metabolic regulation. This conference proposal requests support for attendance and participation by 12 scientists who are currently at the early stages of their careers. Use of funds for this purpose will provide an excellent training opportunity for early-career scientists who will present their work and learn about the latest developments in this burgeoning field. PUBLIC HEALTH RELEVANCE: Project Narrative Regulation of cellular proteins by covalent modifications is fundamental to many biological processes. Over the last several years, emerging evidence suggests that acetylation of proteins controls the ability to perform their cellular functions. This 2009 FASEB summer conference "Histone deacetylases and reversible acetylation in signaling and disease" will focus primarily on the biological pathways and mechanisms of the enzymes that remove this modification, namely the histone deacetylases, or HDACs. There will be particular emphasis on the function of these enzymes in pathways that are associated with age-related diseases, such as neurodegenerative disorders, Alzheimer's and Parkinson's disease, memory loss, diabetes and cancer. In addition to providing a molecular understanding of the roles played by HDACs in gene regulation, there will be an important emphasis on how the enzymes impact central metabolic pathways. Particularly, key topics will include the sirtuins deacetylases, which are metabolically-link deacetylases involved in aging and metabolic regulation. This conference proposal requests support for attendance and participation by 12 scientists who are currently at the early stages of their careers. Use of funds for this purpose will provide an excellent training opportunity for early-career scientists who will present their work and learn about the latest developments in this burgeoning field.