Yang X, Khosravi-Far R, Chang H Y, Baltimore D
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Cell. 1997 Jun 27;89(7):1067-76. doi: 10.1016/s0092-8674(00)80294-9.
The Fas cell surface receptor induces apoptosis upon receptor oligomerization. We have identified a novel signaling protein, termed Daxx, that binds specifically to the Fas death domain. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. A C-terminal portion of Daxx interacts with the Fas death domain, while a different region activates both JNK and apoptosis. The Fas-binding domain of Daxx is a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, while the FADD death domain partially inhibits death but not JNK activation. The Daxx apoptotic pathway is sensitive to both Bcl-2 and dominant-negative JNK pathway components and acts cooperatively with the FADD pathway. Thus, Daxx and FADD define two distinct apoptotic pathways downstream of Fas.
Fas细胞表面受体在受体寡聚化时诱导细胞凋亡。我们鉴定出一种名为Daxx的新型信号蛋白，它能特异性结合Fas死亡结构域。Daxx的过表达增强Fas介导的细胞凋亡并激活Jun氨基末端激酶（JNK）途径。Daxx的C末端部分与Fas死亡结构域相互作用，而不同区域则激活JNK和细胞凋亡。Daxx的Fas结合结构域是Fas诱导的细胞凋亡和JNK激活的显性负性抑制剂，而FADD死亡结构域部分抑制细胞死亡但不抑制JNK激活。Daxx凋亡途径对Bcl-2和显性负性JNK途径成分均敏感，并与FADD途径协同作用。因此，Daxx和FADD定义了Fas下游两条不同的凋亡途径。
