Riley J S, Malik A, Holohan C, Longley D B
Drug Resistance Group, Centre for Cancer Research & Cell Biology, Queen's University Belfast, Belfast, UK.
Cell Death Dis. 2015 Aug 27;6(8):e1866. doi: 10.1038/cddis.2015.213.
Death effector domains (DEDs) are protein-protein interaction domains initially identified in proteins such as FADD, FLIP and caspase-8 involved in regulating apoptosis. Subsequently, these proteins have been shown to have important roles in regulating other forms of cell death, including necroptosis, and in regulating other important cellular processes, including autophagy and inflammation. Moreover, these proteins also have prominent roles in innate and adaptive immunity and during embryonic development. In this article, we review the various roles of DED-containing proteins and discuss recent developments in our understanding of DED complex formation and regulation. We also briefly discuss opportunities to therapeutically target DED complex formation in diseases such as cancer.
死亡效应结构域(DEDs)是最初在诸如FADD、FLIP和caspase-8等参与调节细胞凋亡的蛋白质中鉴定出的蛋白质-蛋白质相互作用结构域。随后,这些蛋白质已被证明在调节其他形式的细胞死亡(包括坏死性凋亡)以及调节其他重要的细胞过程(包括自噬和炎症)中发挥重要作用。此外,这些蛋白质在先天免疫和适应性免疫以及胚胎发育过程中也具有突出作用。在本文中,我们综述了含DED蛋白质的各种作用,并讨论了我们对DED复合物形成和调节理解的最新进展。我们还简要讨论了在癌症等疾病中靶向治疗DED复合物形成的机会。