Apoptosis is specifically induced via signaling through a family of
receptors known collectively as ‘death receptors’ including Fas, TNFR,
DR3, -4 and –5. 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 DR-3 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-kB and induces survival genes including
IAP. Induction of apoptosis via Apo2L requires caspase activity, but the
adaptor requirement is unclearref1,
ref2,
ref3,
ref4,
ref5.
Copyright © 2001-2005 Daniele Focosi.
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