Histone Deacetylases and reversible acetylation in signaling and disease

Summary

Principal Investigator: JOHN DENU
Abstract: 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.
Funding Period: 2009-07-15 - 2010-06-30
more information: NIH RePORT