肿瘤坏死因子相关凋亡诱导配体受体1（DR4）和2（DR5）介导依赖FADD的凋亡信号，并激活核因子κB。

TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB.

作者信息

Schneider P, Thome M, Burns K, Bodmer J L, Hofmann K, Kataoka T, Holler N, Tschopp J

机构信息

Institute of Biochemistry, University of Lausanne, Switzerland.

出版信息

Immunity. 1997 Dec;7(6):831-6. doi: 10.1016/s1074-7613(00)80401-x.

DOI:10.1016/s1074-7613(00)80401-x

PMID:9430228

Abstract

TRAIL induces apoptosis through two closely related receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Here we show that TRAIL-R1 can associate with TRAIL-R2, suggesting that TRAIL may signal through heteroreceptor signaling complexes. Both TRAIL receptors bind the adaptor molecules FADD and TRADD, and both death signals are interrupted by a dominant negative form of FADD and by the FLICE-inhibitory protein FLIP. The recruitment of TRADD may explain the potent activation of NF-kappaB observed by TRAIL receptors. Thus, TRAIL receptors can signal both death and gene transcription, functions reminiscent of those of TNFR1 and TRAMP, two other members of the death receptor family.

摘要

肿瘤坏死因子相关凋亡诱导配体（TRAIL）通过两种密切相关的受体——TRAIL-R1（DR4）和TRAIL-R2（DR5）诱导细胞凋亡。我们在此表明，TRAIL-R1可与TRAIL-R2结合，这提示TRAIL可能通过异源受体信号复合物进行信号传导。两种TRAIL受体均与衔接分子FADD和TRADD结合，且两种死亡信号均被显性负性形式的FADD和FLICE抑制蛋白FLIP阻断。TRADD的募集可能解释了TRAIL受体所观察到的核因子κB的有效激活。因此，TRAIL受体既能发出死亡信号，也能发出基因转录信号，这些功能让人联想到死亡受体家族的另外两个成员——肿瘤坏死因子受体1（TNFR1）和TRAMP的功能。