Extrinsic Activation of Apoptosis
Activation Death Signals (like Fas ligand produced by killer lymphocytes)
Death Receptor proteins (like Fas)
(the clustered Fas proteins recruit intracellular adaptor proteins that bind and
aggregate procaspase-8 molecules, which cleave and activate one another)
DISC (death inducing signaling complex) (this complex is made up is an
aggregation of the Fas receptors, adaptor proteins and procaspass-8 molecules)
XIAP (inhibitor of caspase 3 but not 8)
Caspase 8 Caspase 3
Intrinsic Activation of Apoptosis
Activation by Damage or
Stress
Proaptotic Bcl-2 proteins (like Bax) (these members are activated,
leading to exposure of the pro-apoptoic BH3 domain and translocate to the
mitochondria which induce mitochondria to release proteins like cyotchrome c
contained within the intermembrane space. The transcription of Bcl-2 proteins is
activated due to DNA damage which usually requires
p53)
Mitochondria
Cytochrome C (cytochrome C binds and activates the adaptor protein Apaf-1 below)
Apaf-1
Apoptosome (this complex is cytochrome C, Apaf-1 and now procase-9)
XIAP (inhibits caspase 3 and procaspase 9; The binding and inhibition of
capspases by IAPs is mediated by baculovirus IAP repeats (BIR) domain(s)
present within the IAP. Another region within the IAP, the RING domain acts as a
ubiquitin ligase, protmoting the degradation of the IAP and any caspase bound to
it. Another protein called Smac can relieve this inhibition by binding to
IAPs)
Caspase 9 (now activated this can activate caspase 3)
Caspase 3 Apotosis
Although the pathways above appear to be exclusive, there is actually much crosstalk involved. For example, caspase 8 in the extrinsic pathway can activate another Bcl-2 family member called BID which can also induce cytochrome C release from the mitochondria.