Cell Death 2 Flashcards
One of the targets of caspases includes mediators and regulators of apoptosis. List 5.
Caspases Bid DFF45/ICAD NDUFS1 IAPs
One of the targets of caspases includes structural proteins. List 4.
Nuclear lamins
Catenins
Vimentin
One of the targets of caspases includes cellular DNA repair proteins. List 3.
DNA-PK
Rad51
ATM
One of the targets of caspases includes cell cycle-related proteins. List 3.
p21
Wee1
Rb
Which enzyme cleaves DNA during apoptosis?
CAD (cleaved from iCAD)
What is MOMP?
Mitochondrial Outer Membrane Permeabilisation
What is MOMP mediated/regulated by?
BCL-2 family members
Extrinsic apoptosis features one of three signalling cascades. What are these?
- Death receptor signalling and activation of the caspase-8 to caspase-3 cascade
- Death receptor signalling and activation of the caspase-8 to tBID to MOMP to caspase-9 to caspase-3 pathway
- Ligand deprivation-induced dependence receptor signalling followed by activation of the caspase-9 to caspase-3 cascade.
What are 4 main targets of caspases?
- Mediators/ regulators of apoptosis
- Structural proteins
- Cellular DNA repair proteins
- Cell cycle-related proteins
What is intrinsic apoptosis mediated by?
MOMP (mitochondrial outer membrane permeabilisation)
What is MOMP?
Mitochondrial Outer Membrane Permeabilisation
What three things is intrinsic apoptosis associated with?
- Generalised and irreversible dissipation of mitochondrial membrane potential
- Release of mitochondrial inner membrane space proteins into the cytosol
- Respiratory chain inhibition
What is intrinsic apoptosis triggered by?
Intracellular stress conditions, including: DNA damage Oxidative stress Ca++ overload ER stress (unfolded proteins)
What are the main biochemical features of extrinsic apoptosis by death receptors?
Death receptor signalling
Caspase-8 (-10) activation
BID cleavage and MOMP (in type II)
Caspase-3 (-6,-7) activation
How can extrinsic apoptosis by death receptors be inhibited?
CmA expression
Genetic inhibition of caspases (8&3)
Z-VAD-fmk administration
What are the main biochemical features of extrinsic apoptosis by dependence receptors?
Dependence receptor signalling PP2A activation DAPK1 activation Caspase-9 activation Caspase-3 (-6,-7) activation
How can extrinsic apoptosis by dependence receptors be inhibited?
Genetic inhibition of caspases (9 & 3)
Genetic inhibition of PP2A
Z-VAD-fmk administration
What are the main biochemical features of caspase-dependent intrinsic apoptosis?
MOMP
Irreversible mitochondrial transmembrane dissipation
How can caspase-dependent intrinsic apoptosis be inhibited?
BCL-2 over expression
Z-VAD-fmk administration
What are the main biochemical features of caspase-independent intrinsic apoptosis?
Release of IMS proteins
Respiratory chain inhibition