Seyrek Kamil, Ivanisenko Nikita V, Richter Max, Hillert Laura K, König Corinna, Lavrik Inna N
Translational Inflammation Research, Medical Faculty, Otto von Guericke University, Magdeburg, Germany.
The Federal Research Center Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.
Trends Cell Biol. 2020 May;30(5):354-369. doi: 10.1016/j.tcb.2020.02.006. Epub 2020 Mar 29.
Apoptosis is a form of programmed cell death, deregulation of which occurs in multiple disorders, including neurodegenerative and autoimmune diseases as well as cancer. The formation of a death-inducing signaling complex (DISC) and death effector domain (DED) filaments are critical for initiation of the extrinsic apoptotic pathway. Post-translational modifications (PTMs) of DED-containing DISC components such as FADD, procaspase-8, and c-FLIP comprise an additional level of apoptosis regulation, which is necessary to overcome the threshold for apoptosis induction. In this review we discuss the influence of PTMs of FADD, procaspase-8, and c-FLIP on DED filament assembly and cell death induction, with a focus on the 3D organization of the DED filament.
细胞凋亡是一种程序性细胞死亡形式，其失调发生在多种疾病中，包括神经退行性疾病、自身免疫性疾病以及癌症。死亡诱导信号复合物（DISC）的形成和死亡效应结构域（DED）细丝对于外源性凋亡途径的启动至关重要。含DED的DISC组分（如FADD、procaspase-8和c-FLIP）的翻译后修饰（PTM）构成了细胞凋亡调节的另一个层面，这对于克服细胞凋亡诱导阈值是必要的。在本综述中，我们讨论了FADD、procaspase-8和c-FLIP的PTM对DED细丝组装和细胞死亡诱导的影响，重点关注DED细丝的三维组织。
