The c-FLIP-NH2 terminus (p22-FLIP) induces NF-κB activation

被引:158
作者
Golks, Alexander [1 ]
Brenner, Dirk [1 ]
Krammer, Peter H. [1 ]
Lavrik, Inna N. [1 ]
机构
[1] German Canc Res Ctr, Div Immunogenet, Tumorimmunol Program, D-69120 Heidelberg, Germany
关键词
D O I
10.1084/jem.20051556
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
c-FLIP proteins (isoforms: c-FLIPL, c-FLIPS, and c-FLIPR) play an essential role in the regulation of death receptor - induced apoptosis. Here, we demonstrate that the cytoplasmic NH2-terminal procaspase-8 cleavage product of c-FLIP (p22-FLIP) found in nonapoptotic malignant cells, primary T and B cells, and mature dendritic cells (DCs) strongly induces nuclear factor kappa B (NF-kappa B) activity by interacting with the I kappa B kinase (IKK) complex via the IKK gamma subunit. Thus, in addition to inhibiting apoptosis by binding to the death-inducing signaling complex, our data demonstrate a novel mechanism by which c-FLIP controls NF-kappa B activation and life/death decisions in lymphocytes and DCs.
引用
收藏
页码:1295 / 1305
页数:11
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