Siegmund Daniela, Lang Isabell, Wajant Harald
Division of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University Hospital Würzburg, Germany.
FEBS J. 2017 Apr;284(8):1131-1159. doi: 10.1111/febs.13968. Epub 2016 Dec 14.
Since their identification more than 20 years ago, the death receptors CD95, TRAILR1, and TRAILR2 have been intensively studied with respect to their cell death-inducing activities. These receptors, however, can also trigger a variety of cell death-independent cellular responses reaching from the activation of proinflammatory gene transcription programs over the stimulation of proliferation and differentiation to induction of cell migration. The cell death-inducing signaling mechanisms of CD95 and the TRAIL death receptors are well understood. In contrast, despite the increasing recognition of the biological and pathophysiological relevance of the cell death-independent activities of CD95, TRAILR1, and TRAILR2, the corresponding signaling mechanisms are less understood and give no fully coherent picture. This review is focused on the cell death-independent activities of CD95 and the TRAIL death receptors and addresses mainly three questions: (a) how are these receptors linked to noncell death pathways at the molecular level, (b) which factors determine the balance of cell death and cell death-independent activities of CD95 and the TRAIL death receptors at the cellular level, and (c) what are the consequences of the cell death-independent functions of these receptors for their role in cancer and inflammatory diseases.
自20多年前被发现以来，死亡受体CD95、TRAILR1和TRAILR2因其诱导细胞死亡的活性而受到深入研究。然而，这些受体也能触发多种不依赖细胞死亡的细胞反应，从促炎基因转录程序的激活到增殖和分化的刺激，再到细胞迁移的诱导。CD95和TRAIL死亡受体诱导细胞死亡的信号传导机制已得到充分了解。相比之下，尽管人们越来越认识到CD95、TRAILR1和TRAILR2不依赖细胞死亡的活性在生物学和病理生理学上的相关性，但其相应的信号传导机制仍了解较少，且尚未形成完全连贯的图景。本综述聚焦于CD95和TRAIL死亡受体不依赖细胞死亡的活性，主要探讨三个问题：(a) 这些受体在分子水平上如何与非细胞死亡途径相连？(b) 哪些因素在细胞水平上决定了CD95和TRAIL死亡受体细胞死亡和不依赖细胞死亡活性的平衡？(c) 这些受体不依赖细胞死亡的功能对其在癌症和炎症性疾病中的作用有何影响？
