Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8

被引:288
作者
Sprick, MR
Rieser, E
Stahl, H
Grosse-Wilde, A
Weigand, MA
Walczak, H [1 ]
机构
[1] DKFZ, Tumour Immunol Program, Div Apoptosis Regulat, Heidelberg, Germany
[2] Univ Heidelberg, Clin Anaesthesiol, D-69120 Heidelberg, Germany
关键词
caspase; CD95 (APO-1/Fas); death-inducing signalling complex; death receptor; TRAIL;
D O I
10.1093/emboj/cdf441
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The involvement of the death adaptor protein FADD and the apoptosis-initiating caspase-8 in CD95 and TRAIL death signalling has recently been demonstrated by the analysis of the native death-inducing signalling complex (DISC) that forms upon ligand-induced receptor cross-linking. However, the role of caspase-10, the other death-effector-domain-containing caspase besides caspase-8, in death receptor signalling has been controversial. Here we show that caspase-10 is recruited not only to the native TRAIL DISC but also to the native CD95 DISC, and that FADD is necessary for its recruitment to and activation at these two protein complexes. With respect to the function of caspase-10, we show that it is not required for apoptosis induction. In addition, caspase-10 can not substitute for caspase-8, as the defect in apoptosis induction observed in caspase-8-deficient cells could not be rescued by overexpression of caspase-10. Finally, we demonstrate that caspase-10 is cleaved during CD95-induced apoptosis of activated T cells. These results show that caspase-10 activation occurs in primary cells, but that its function differs from that of caspase-8.
引用
收藏
页码:4520 / 4530
页数:11
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