死亡受體的信號通路圖

死亡受體(death receptor)包括多種分子。有關死亡受體及其配體的研究是目前細胞凋亡 研究的熱點之一。死亡受體均屬TNFR 基因超家族，它們有相似的富含半胱氨酸的胞外結構域。死亡受體都含有同源的胞漿內序列，稱為死亡結構域(death domain)或死亡區，其主要功能是介導死亡受體誘發的細胞凋亡。目前所知的死亡受體主要有Fas、TNFR1、CAR1、NGFR、DR3、DR4、DR5 等。激活這些受體的配體為TNF 基因超家族，有FasL、TNF、Apo3L、Apo-2L(TNF 相關凋亡誘導配體)等，還不斷有新的配體發現。死亡配體與死亡受體結合，通過死亡結構域激發細胞凋亡機制。

Apoptosis is specifically induced via signaling through a family of receptors known collectively as ?death 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.