Apoptosis regulation - BCL-2 family and cell death pathways
Core concept
- Two routes converge on the executioner caspases 3, 6, 7
A. Intrinsic (mitochondrial)
- Trigger: DNA damage, hypoxia, growth factor withdrawal, oncogene stress
- p53 -> inc BH3-only proteins
- -> BAX/BAK oligomerise -> MOMP (mitochondrial outer membrane permeabilisation)
- -> cytochrome c released -> + APAF-1 + procaspase-9 = apoptosome -> caspase 9 -> caspase 3
- SMAC/DIABLO also released -> neutralises the IAPs that brake caspases
B. Extrinsic (death receptor)
- Fas/FasL, TNFR1, TRAIL -> FADD -> DISC -> caspase 8 -> caspase 3
- Caspase 8 also cleaves Bid -> tBid -> feeds into the intrinsic pathway for amplification
C. Granzyme B
- Delivered by CTL/NK through perforin pores -> activates caspase 3 directly, bypassing both
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