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

虽然我们细胞中的大部分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自杀的天然途径，称为细胞凋亡。当细胞遭受不可修复的DNA损伤时，细胞凋亡就会发生，这可以被认为是一个利他主义的决定-通过牺牲一个来拯救生物体。细胞凋亡通常是一个“沉默”的事件，并且不伴随着细胞向免疫细胞发出任何危险信号，这可能发生在细胞因细菌或病毒感染而死亡时。事实上，非“沉默”的凋亡性细胞死亡可导致诸如自身免疫性疾病的病症。细胞凋亡如何保持免疫学沉默事件尚不清楚。我们发现了一种称为DYRK 2的细胞蛋白，它似乎参与促进自然凋亡，同时减少细胞免疫反应。因此，我们已经确定了一种参与共调节这两个过程的蛋白质。我们在本申请中的目标是鉴定参与该途径的其他细胞蛋白，这将阐明细胞内以前未被认识到的调节机制。

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.