Chinnaiyan A M, O'Rourke K, Tewari M, Dixit V M
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Cell. 1995 May 19;81(4):505-12. doi: 10.1016/0092-8674(95)90071-3.
Using the cytoplasmic domain of Fas in the yeast two-hybrid system, we have identified a novel interacting protein, FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8. FADD contains a death domain homologous to the death domains of Fas and TNFR-1. A point mutation in FADD, analogous to the lpr mutation of Fas, abolishes its ability to bind Fas, suggesting a death domain to death domain interaction. Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme. These findings suggest that FADD may play an important role in the proximal signal transduction of Fas.
利用酵母双杂交系统中的Fas胞质结构域，我们鉴定出一种新型相互作用蛋白FADD，它能结合Fas以及Fas-FD5（一种具有增强杀伤活性的Fas突变体），但不结合功能失活的突变体Fas-LPR和Fas-FD8。FADD含有一个与Fas和TNFR-1的死亡结构域同源的死亡结构域。FADD中的一个点突变，类似于Fas的lpr突变，消除了其结合Fas的能力，提示存在死亡结构域与死亡结构域的相互作用。FADD在MCF7和BJAB细胞中的过表达诱导细胞凋亡，这种凋亡，如同Fas诱导的凋亡一样，被白细胞介素-1β转换酶的特异性抑制剂CrmA所阻断。这些发现提示FADD可能在Fas的近端信号转导中起重要作用。
