NAD Metabolism and Signaling

NAD 代谢和信号传导

• 批准号: 8196505
• 负责人: MYRON K JACOBSON
• 金额: $ 0.8万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196505
• 关键词: ADP Ribose Transferases; ADP ribosylation; ADP-ribosyl Cyclase; Address; Affect; Aging; Anabolism; Antineoplastic Agents; Apoptosis; Area; Award; Biochemistry; Biology; Biology of Aging; Calcium; Cancer Biology; Cell Survival; Cell physiology; Cells; Cellular Stress; Cellular biology; Collaborations; Complex; DNA Repair; Development; Diabetes Mellitus; Disease; Energy Metabolism; Ensure; Enzymatic Biochemistry; Enzymes; Faculty; Fees; Financial Support; Fostering; Funding; Gene Expression Regulation; Gene Silencing; Genetic Transcription; Genotoxic Stress; Goals; Health; Immunology; Individual; Inflammation; Lead; Longevity; Lysine; Malignant Neoplasms; Mediating; Metabolic syndrome; Metabolism; Mission; Mitosis; Mono(ADP-Ribose) Transferases; Mono-S; NADH; NADP; Niacinamide; Nicotinamide adenine dinucleotide; Obesity; Oral; Participant; Pathway interactions; Personal Satisfaction; Physiology; Play; Poly(ADP-ribose) Polymerases; Postdoctoral Fellow; Principal Investigator; Process; Proteins; Public Health; Qualifying; Reaction; Reporting; Research; Research Personnel; Role; Scholarship; Science; Scientist; Selection Criteria; Signal Transduction; Sirtuins; Students; System; Therapeutic; Translational Research; Travel; Underrepresented Minority; United States; United States National Institutes of Health; Woman; Work; Writing; abstracting; biological adaptation to stress; clinical application; drug discovery; insight; interdisciplinary approach; meetings; migration; novel diagnostics; nutrition; programs; response; structural biology; symposium

DESCRIPTION (provided by applicant): The vitamin B3-derived metabolite, nicotinamide adenine dinucleotide (NAD), and its related metabolites, NADH, NADP and NADPH, are best known as co-enzymes for hydride transfer enzymes that play central roles in cellular energy metabolism. It was largely believed that NAD and its related metabolites were too abundant to function in a signal transduction capacity and that they were therefore unlikely to be involved in regulating cellular functions. However, with the more recent discoveries showing that NAD is consumed by enzymes that deacetylate lysine and generate putative signaling metabolites (sirtuins), that post-translationally modify protein targets by ADP-ribosylation via poly ADP ribose polymerases (PARPs) and mono ADP ribosyltransferases (ARTs) and that regulate cell signaling by generating calcium-mobilizing metabolites from NAD and NADP (CD38 and ADP-ribosyl cyclases), it is now clear that NAD metabolism plays a more complex role in cells than previously appreciated. Indeed, the enzymes that catabolize NAD as well as those that contribute to its synthesis and salvage are now known to be global regulators in key aspects of biology from DNA repair to gene transcription and from cancer biology to aging. Recent research has highlighted the many ways in which these NAD-dependent processes intersect, making it clear that a more global systems-wide view of NAD metabolism is central to understanding how the individual processes are regulated. Although scientists can attend conferences that focus on a single aspect of NAD biology, conferences that focus on the NAD metabolome as a whole are not readily available. Thus, there is a need for a conference that brings together the leading scientists working in all areas of the NAD metabolome. The upcoming FASEB summer conference "NAD metabolism and signaling" will meet this need by covering all aspects of NAD biology. Participants and speakers will include those working in the areas of NAD enzymology, biochemistry, signal transduction, structural biology, DNA repair, transcription, nutrition, cell biology, physiology, immunology/inflammation, cancer biology, aging and clinical applications that include a new paradigm for cancer drug discovery. Topics covered in the meeting will include NAD biosynthesis and metabolism, sirtuin, PARP, ART and CD38-mediated signaling and gene regulation, NAD-dependent crosstalk and therapeutic modulation of the NAD metabolome. The major goals of this conference are to foster new interactions between scientists that do not normally meet one another in the course of their work and to promote interdisciplinary interactions that will lead to new collaborations that will advance the field and facilitate development of new therapies. We expect that the scientific insights generated during the course of this meeting will result in the beginning of a systems-wide approach to evaluating the role of the NAD metabolome in cancer, aging, metabolic syndrome and inflammation. The objective of this proposal is to seek funds to support the conference fees for outstanding young investigators, with a particular emphasis on individuals that are under-represented in science. PUBLIC HEALTH RELEVANCE: The proposed meeting "NAD metabolism and signaling" is relevant to public health in that it will focus on establishing the cornerstones for a systems-wide approach to evaluating the role of the NAD metabolome in cancer, aging, obesity and inflammation. This is important to the mission of the NIH because the insights gained from this meeting may lead to the development of new diagnostics and treatments for diseases such as cancer and diabetes that affect the health and well-being of all US citizens.

性状（由申请方提供）：维生素B3衍生代谢物烟酰胺腺嘌呤二核苷酸（NAD）及其相关代谢物NADH、NADP和NADPH是最知名的氢化物转移酶的辅酶，在细胞能量代谢中发挥核心作用。人们普遍认为，NAD及其相关代谢物太丰富，无法发挥信号转导能力，因此它们不太可能参与调节细胞功能。然而，随着最近的发现表明NAD被脱乙酰赖氨酸并产生推定的信号代谢物的酶消耗，（sirtuins），其通过经由聚ADP核糖聚合酶（PARP）和单ADP核糖基转移酶（ART）的ADP-核糖基化来对蛋白质靶标进行后修饰，并且通过从NAD和NADP产生钙动员代谢物来调节细胞信号传导（CD 38和ADP-核糖基环化酶），现在清楚的是，NAD代谢在细胞中起着比以前认识到的更复杂的作用。事实上，现在已知分解代谢NAD的酶以及有助于其合成和挽救的酶是生物学关键方面的全球调节剂，从DNA修复到基因转录，从癌症生物学到衰老。最近的研究强调了这些NAD依赖性过程交叉的许多方式，清楚地表明，NAD代谢的更全球性的系统范围的观点对于理解单个过程是如何调节的至关重要。虽然科学家们可以参加专注于NAD生物学单个方面的会议，但专注于NAD代谢组整体的会议并不容易获得。因此，有必要召开一次会议，汇集在NAD代谢组学所有领域工作的领先科学家。即将举行的FASEB夏季会议“NAD代谢和信号”将通过涵盖NAD生物学的各个方面来满足这一需求。与会者和发言者将包括那些在NAD酶学，生物化学，信号转导，结构生物学，DNA修复，转录，营养，细胞生物学，生理学，免疫学/炎症，癌症生物学，衰老和临床应用领域的工作，包括癌症药物发现的新范式。会议涵盖的主题将包括NAD生物合成和代谢、沉默调节蛋白、PARP、ART和CD 38介导的信号传导和基因调节、NAD依赖性串扰和NAD代谢组的治疗调节。本次会议的主要目标是促进科学家之间的新的互动，这些科学家通常不会在他们的工作过程中相互见面，并促进跨学科的互动，这将导致新的合作，从而推动该领域的发展并促进新疗法的发展。我们预计，在本次会议期间产生的科学见解将导致一个系统范围的方法来评估NAD代谢组在癌症，衰老，代谢综合征和炎症中的作用的开始。这项提案的目的是寻求资金，以支持杰出的年轻研究人员的会议费，特别强调在科学领域代表性不足的个人。 公共卫生关系：拟议的会议“NAD代谢和信号”与公共卫生有关，因为它将侧重于建立全系统方法的基石，以评估NAD代谢组在癌症、衰老、肥胖和炎症中的作用。这对NIH的使命很重要，因为从这次会议中获得的见解可能会导致对影响所有美国公民健康和福祉的癌症和糖尿病等疾病的新诊断和治疗的发展。