Untitled - D Ank Unlimited

apoptosis, caspase pathway 74 apoptosis, immunotoxin-induced
Removal of a cytokine required for cellular viability leads to the following sequential events: (1) loss of kinase (AKT) activity; (2) dephosphorylation of Bad
(or some other regulator of Bcl-2/Bcl-x activity); (3) Bad binding to Bcl-2; (4) loss of normal mitochondrial physiology; (5) release of cytochrome c; (6) binding
of cytochrome c by Apaf-1 with concomitant activation of caspase 9; (7) amplification by the caspase cascade; (8) cleavage of vital cellular proteins; (9) fission of
cells into apoptotic bodies; and finally (10) disappearance of any trace of the cell when the apoptotic bodies are engulfed by either neighboring or phagocytic cells.
apoptosis, caspase pathway
A group of intracellular proteases called caspases are
responsible for the deliberate disassembly of cells into apoptotic
bodies during apoptosis. Caspases are present as inactive
proenzymes activated by proteolytic cleavage. Caspases
8, 9, and 3 are situated at pivotal junctions in apoptosis
pathways. Caspase 8 initiates disassembly in response to
extracellular apoptosis-inducing ligands and is activated in
a complex associated with the cytoplasmic death domains
of many cell surface receptors for the ligands. Caspase 9
activates disassembly in response to agents or insults that
trigger the release of cytochrome c from mitochondria
and is activated when complexed with apoptotic protease
activating factor 1 (APAF-1) and extramitochondrial
cytochrome c. Caspase 3 appears to amplify caspase 8 and
caspase 9 initiation signals into full-fledged commitments
to disassembly. Caspase 8 and caspase 9 activate caspase
3 by proteolytic cleavage, and caspase 3 then cleaves vital
cellular proteins or other caspases.
apoptosis, immunotoxin-induced
Immunotoxins are cytotoxic agents usually assembled as
recombinant fusion proteins composed of targeting domains
and toxins. The targeting domain controls the specificity of
action and is usually derived from an antibody Fv fragment,
a growth factor, or a soluble receptor. The protein toxins
are obtained from bacteria (e.g., Pseudomonas endotoxin
[PE] or diphtheria toxin [DT]) or from plants (e.g., ricin).
Immunotoxins have been studied as treatments for cancer,
graft-vs.-host disease, autoimmune disease, and AIDS.
The PE and DT bacterial toxins act via the ADP ribosylation
of elongation factor 2, thereby inactivating it. This
results in the arrest of protein synthesis and subsequent cell
death. These toxins can also induce apoptosis, although the
mechanism is unknown. Two common features of apoptotic
cell death are the activation of a group of cysteine proteases
called caspases and the caspase-catalyzed cleavage
TNF-induced receptor trimerization aggregates the death domains
(DD) of tumor necrosis factor (TNF) RI and recruits the adaptor protein
TRADD. This in turn promotes the recruitment of the DD-containing
cytoplasmic proteins FADD, TRAF2, and RIP to form an active TNF RI
signaling complex. The active TNF RI signaling complex can then recruit
procaspase 8. Following activation, caspase 8 can initiate caspasemediated
cell death.
of so-called “death substrates” such as the nuclear repair
enzyme poly (ADP-ribose) polymerase (PARP).