死亡受体的信号通路图
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- 细胞凋亡专题
死亡受体(death receptor)包括多种分子。有关死亡受体及其配体的研究是目前细胞凋亡 研究的热点之一。死亡受体均属TNFR 基因超家族，它们有相似的富含半胱氨酸的胞外结构域。死亡受体都含有同源的胞浆内序列，称为死亡结构域(death domain)或死亡区，其主要功能是介导死亡受体诱发的细胞凋亡。目前所知的死亡受体主要有Fas、TNFR1、CAR1、NGFR、DR3、DR4、DR5 等。激活这些受体的配体为TNF 基因超家族，有FasL、TNF、Apo3L、Apo-2L(TNF 相关凋亡诱导配体)等，还不断有新的配体发现。死亡配体与死亡受体结合，通过死亡结构域激发细胞凋亡机制。
Apoptosis is specifically induced via signaling through a family of receptors known collectively as ødeath receptorsÓ including Fas, TNFR, DR3, DR4 and DR5. Death receptor ligands characteristically initiate signaling via receptor oligomerization, recruitment of specialized adaptor proteins and activation of caspase cascades. FasL binding induces Fas trimerization and recruits initiator caspase 8 via the adapter protein FADD. Caspase 8 then oligomerizes and is activated via autocatalysis. Activated caspase 8 stimulates apoptosis via two parallel cascades: it directly cleaves and activates caspase-3, and it cleaves Bid (a Bcl-2 family protein). Truncated Bid (tBid) translocates to mitochondria, inducing cytochrome c release, which sequentially activates caspases 9 and 3. TNF and DR-3L can deliver pro- or anti-apoptotic signals. TNFR and DR3 promote apoptosis via the adaptor proteins TRADD/FADD and the activation of caspase 8. Alternatively, apoptosis is inhibited via an adaptor protein complex including RIP which activates NF-ÁB and induces survival genes including IAP. Induction of apoptosis via Apo2L requires caspase activity, but the adaptor requirement is unclear.
