Metabolic signals regulating cell growth versus survival

项目摘要/摘要： 在上一次供资期间，研究表明，含硫氨基酸蛋氨酸 是氨基酸充足的关键信号。蛋氨酸通过促进其合成发挥作用 作为生物甲基供体的下游代谢产物S-腺苷蛋氨酸 许多对生命至关重要的单碳转移反应。此应用程序建议 全面研究蛋氨酸和SAM作用机制 调节重要的细胞通路，平衡细胞生长和存活 新陈代谢状态。遗传学和生物化学的结合将被用来阐明 蛋氨酸和SAM调节基于磷酸化的信号转导，表观遗传甲基化 染色质的修饰以及硫代谢的转录和翻译 基因。这些研究的洞察力将有助于了解这些前哨代谢物的作用。 在老龄化和与年龄相关的疾病方面。

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.