DYRK2 co-regulates apoptosis and innate immunity in response to genotoxic stress

DYRK2 共同调节细胞凋亡和先天免疫以应对基因毒性应激

• 批准号: RGPIN-2014-04810
• 负责人: Parks, Robin
• 金额: $ 3.42万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629529
• 关键词: DYRK2; co; regulates; apoptosis; innate

Although much of the programmed information in our cells is dedicated to carrying out the fundamental processes necessary for life, our cells also possess a natural pathway for committing suicide, referred to as apoptosis. Apoptosis can occur when the cell sustains irreparable DNA damage, and can be thought of as an altruistic decision – save the organism by sacrificing the one. Apoptosis is typically a “silent” event, and is not accompanied by the cell emitting any danger signals to immune cells, as might occur when a cell dies due to infection with a bacteria or virus. Indeed, apoptotic cell death that is not “silent” can result in disorders such as autoimmune disease. How apoptosis remains an immunologically silent event is not known. We have uncovered a cellular protein termed DYRK2 which seems to be involved in promoting natural apoptosis while simultaneously diminishing the cells immune response. Thus, we have identified a protein involved in co-regulating these two processes. Our goal in this application is to identify other cellular proteins involved in this pathway, which will elucidate a previously unappreciated regulator mechanism within the cell.

尽管我们细胞中的许多程序化信息都致力于执行生命所必需的基本过程，但我们的细胞也拥有一条自杀的自然途径，称为细胞凋亡。当细胞遭受无法修复的DNA损伤时，就会发生细胞凋亡，这可以被认为是一种利他主义的决定--牺牲一个人来拯救有机体。细胞凋亡通常是一种“沉默的”事件，并不伴随着细胞向免疫细胞发出任何危险信号，当细胞因感染细菌或病毒而死亡时可能会发生这种情况。事实上，非“沉默”的细胞凋亡性死亡会导致自身免疫性疾病等疾病。细胞凋亡是如何在免疫上保持沉默的尚不清楚。我们发现了一种名为DYRK2的细胞蛋白，它似乎参与了促进自然细胞凋亡，同时降低细胞免疫反应的过程。因此，我们已经确定了一种参与共同调节这两个过程的蛋白质。我们在这一应用中的目标是确定参与这一途径的其他细胞蛋白，这将阐明细胞内以前未被认识的调节机制。