Golks A, Brenner D, Schmitz I, Watzl C, Krueger A, Krammer P H, Lavrik I N
Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Cell Death Differ. 2006 Mar;13(3):489-98. doi: 10.1038/sj.cdd.4401766.
Formation of the CD95 (APO-1/Fas) death inducing signaling complex (DISC) plays a central role in CD95 signaling. Previously, CD95 DISC composition was analyzed by two-dimensional gel electrophoresis and four major cytotoxicity-associated proteins (CAP1-4) were found. CAP1 and CAP2 were defined to be unmodified and phosphorylated FADD, respectively. CAP4 was identified as procaspase-8a. CAP3, however, has remained elusive. In this study, we demonstrate that CAP3 is an intermediate of procaspase-8 processing. CAP3 is generated within seconds of DISC formation and subsequently processed to the prodomain of procaspase-8a that is known as p26 (CAP5). These findings lead to new insights into the mechanism of procaspase-8 processing and apoptosis initiation.
CD95（APO-1/Fas）死亡诱导信号复合物（DISC）的形成在CD95信号传导中起核心作用。此前，通过二维凝胶电泳分析了CD95 DISC的组成，发现了四种主要的细胞毒性相关蛋白（CAP1-4）。CAP1和CAP2分别被定义为未修饰的和磷酸化的FADD。CAP4被鉴定为procaspase-8a。然而，CAP3的身份一直不明。在本研究中，我们证明CAP3是procaspase-8加工过程的一个中间体。CAP3在DISC形成后的几秒钟内产生，随后被加工成procaspase-8a的前结构域，即众所周知的p26（CAP5）。这些发现为procaspase-8加工和细胞凋亡起始机制带来了新的见解。
