Apoptosis, or programmed cell death, is a regulated physiological process
leading to cell death characterized by cell shrinkage, membrane blebbing
and DNA fragmentation. Caspases, a family of cysteine proteases, are central
regulators of apoptosis. Initiator caspases (including 8, 9, 10 and 12)
are closely coupled to pro-apototic signals. Once activated, these caspases
cleave and activate downstream effector caspases (including 3, 6 and 7)
which in turn cleave cytoskeletal and nuclear proteins and induce apoptosis.
Cytochrome C released from mitochondria is coupled to the activation of
caspase 9, a key initiator caspase. Pro-apoptotic stimuli include the FasL,
TNF, DNA damage and ER stress. Fas and the TNFR activate caspases 8 and
10; DNA damage leads to the activation of caspase 9; and ER stress leads
to the calcium-mediated activation of caspase 12. Anti-apoptotic ligands
including growth factors and cytokines activate AKT and p90RSK,
which inhibit Bad and prevent cytochrome C release. TNFR can also stimulate
an anti-apoptotic pathway by inducing IAP, which directly inhibits caspases
3, 7 and 9ref1,
ref2,
ref3.
Copyright © 2001-2004 Daniele Focosi.
All rights reserved
| Terms of use |
Legal
notices
