Metabolic signals regulating cell growth versus survival

项目概要/摘要： 在上一个资助期，研究表明，含硫氨基酸蛋氨酸 是氨基酸充足的关键信号。蛋氨酸的功能是促进其 下游代谢物S-腺苷甲硫氨酸，其作为生物甲基供体， 许多对生命至关重要的一碳转移反应。本申请建议 全面研究蛋氨酸和SAM发挥作用的机制， 调节重要的细胞途径，以平衡细胞生长与存活， 代谢状态遗传学和生物化学的结合将被用来阐明如何 蛋氨酸和SAM调节基于磷酸化的信号传导，表观遗传甲基化 染色质上的修饰，以及硫代谢的转录和翻译 基因.从这些研究中获得的见解将为这些哨兵代谢物的作用提供信息 衰老和与年龄有关的疾病。

Project Summary/Abstract: Over the previous funding period, it was shown that the sulfur-containing amino acid methionine is a key signal of amino acid sufficiency. Methionine functions by boosting the synthesis of its downstream metabolite S-adenosylmethionine, which serves as the biological methyl donor in many one-carbon transfer reactions critical for life. This application proposes to comprehensively investigate the mechanisms by which methionine and SAM function to regulate important cellular pathways in balancing cell growth versus survival in response to metabolic state. A combination of genetics and biochemistry will be utilized to elucidate how methionine and SAM regulate phosphorylation-based signaling, epigenetic methylation modifications on chromatin, as well as the transcription and translation of sulfur metabolism genes. Insights from these studies will be informative as to the role of these sentinel metabolites in aging and age-related diseases.