The "fuzzy logic" of the death-inducing signaling complex in lymphocytes.
The "fuzzy logic" of the death-inducing signaling complex in lymphocytes.
复制标题
淋巴细胞中死亡诱导信号复合物的“模糊逻辑”。
DOI：
10.1023/a:1025313415487
复制
发表时间：
2003
影响因子：
9.1
通讯作者：
Arechiga,AdrianF
中科院分区：
文献类型：
--
作者：
Walsh,CraigM;Luhrs,KeithA;Arechiga,AdrianF
Receptors belonging to the tumor necrosis factor receptor family have long been thought to play an important role in the regulation of immunity. Although this family is composed of a large number of surface receptors that potentiate myriad functionsin vivo, a subset is known to directly convey apoptotic signals. One such molecule belonging to this subset is CD95. Ligation of CD95 instigates the formation of a complex known as the “death-inducing signaling complex” or DISC, which is composed of molecules including FADD (Fas associated with death domain) and RIP (receptor-interacting kinase), as well as procaspases-8 and -10, and a caspase-8-like molecule that lacks proteolytic activity called c-FLIP. Although the DISC was initially thought to serve an exclusively proapoptotic role, humans and mice with defects in various components of this complex demonstrate a variety of developmental and hematopoietic defects that are not apparently due to aberrant apoptosis. These findings paint a far more complex picture of the numerous components of the DISC, and provide evidence that these complexes serve nonapoptotic functions. Herein, we summarize the experimental evidence challenging the notion that the DISC imparts an exclusively apoptotic function and provide hypotheses to account for these alternative roles. Rather than operating as a binary system, we propose that the DISCs formed around various DRs transduce signals leading to a variety of cellular fates.
