University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96813, USA.
Student Research Experience Program of University of Hawaii, Honolulu, HI 96822, USA.
Int J Mol Sci. 2021 Nov 30;22(23):12976. doi: 10.3390/ijms222312976.
Among human genetic diseases, Fanconi Anemia (FA) tops all with its largest number of health complications in nearly all human organ systems, suggesting the significant roles played by FA genes in the maintenance of human health. With the accumulated research on FA, the encoded protein products by FA genes have been building up to the biggest cell defense signaling network, composed of not only 22+ FA proteins but also ATM, ATR, and many other non-FA proteins. The FA D2 group protein (FANCD2) and its paralog form the focal point of FA signaling to converge the effects of its upstream players in response to a variety of cellular insults and simultaneously with downstream players to protect humans from contracting diseases, including aging and cancer. In this review, we update and discuss how the FA signaling crucially eases cellular stresses through understanding its focal point.
在人类遗传疾病中,范可尼贫血症(FA)因其几乎影响所有人类器官系统的大量健康并发症而位居榜首,这表明 FA 基因在维持人类健康方面发挥着重要作用。随着对 FA 的研究积累,FA 基因编码的蛋白产物逐渐形成了最大的细胞防御信号网络,不仅由 22 多种 FA 蛋白组成,还包括 ATM、ATR 和许多其他非 FA 蛋白。FA D2 组蛋白(FANCD2)及其同源物是 FA 信号的焦点,它汇聚了其上游参与者在应对各种细胞应激时的作用,并与下游参与者协同作用,保护人类免受疾病的侵害,包括衰老和癌症。在这篇综述中,我们更新并讨论了 FA 信号如何通过了解其焦点来关键地缓解细胞应激。