Regulation of the ER Stress Response by Amino Acids

氨基酸对内质网应激反应的调节

• 批准号: 402127-2013
• 负责人: Kristof, Arnold
• 金额: $ 3.13万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=596052
• 关键词: Regulation; ER; Stress; Response; Amino

The long term objective of this research program is to determine how individual building blocks of proteins (i.e., amino acids) control adaptive survival responses in cells. In this proposal, we investigate how the availability of amino acids controls the 'endoplasmic reticulum stress response', an ancient cellular process that controls the balance between life and death. We predict that the availability of amino acids will modify the function of 'endoplasmic reticulum stress' transcription factors and genes that regulate cell death. The short term objective of this research proposal is to identify and characterize the proteins required for amino acids sensing during the endoplasmic reticulum stress response, and how they are modified by amino acid depletion. We will use sophisticated biochemical and molecular biology techniques to measure the effect of amino acids on the modification and levels of endoplasmic reticulum stress proteins, and on cell death. Our studies will reveal new mechanisms by which nutritional components control cellular adaptive responses to stress, and how cells make decisions about their survival.

这项研究计划的长期目标是确定蛋白质的各个组成部分（即，氨基酸）控制细胞中的适应性存活反应。在这个提议中，我们研究了氨基酸的可用性如何控制“内质网应激反应”，这是一个古老的细胞过程，控制着生与死之间的平衡。我们预测，氨基酸的可用性将改变“内质网应激”转录因子和调控细胞死亡的基因的功能。这项研究的短期目标是确定和表征内质网应激反应过程中氨基酸传感所需的蛋白质，以及它们如何通过氨基酸消耗进行修饰。我们将使用复杂的生化和分子生物学技术来测量氨基酸对内质网应激蛋白的修饰和水平以及对细胞死亡的影响。我们的研究将揭示营养成分控制细胞对压力的适应性反应的新机制，以及细胞如何决定它们的生存。