Resistance to cell death Flashcards
what affects the net number of cells in the body
balance between cell growth and apoptosis
what enzymes are the key players in apoptosis?
caspases
what does caspaces catalyse?
proteolysis to help breakdown cellular components for disposal
what does defects in apoptosis influence the effectiveness of?
the drugs which exert their effect by inducing apoptosis
external induction of apoptosis
by death factors
internal inducers of apoptosis
physical or chemical insults such as DNA damage or oxidative stress
which two pathways can be activated to cause apoptosis?
extrinsic
intrinsic
caspases work by cleaving where on proteins?
proteolysis at aspartate residues
TF: caspases are central to the intrinsic pathways only
false
central in both
how many mammalian caspases have been identified so far?
13
how are caspases synthesised?
as inactive enzymes called procaspases
how do procaspases get activated
by cleavage at aspartate residues
what are the class of receptors on the cell membrane which are related to apoptosis called?
death receptors
examples of death factors and their ligands
Fas ligand- Fas receptor
tumour necrosis factor ligand - TNF receptor
how is TNF found compared to Fas ligand
TNF is a soluble factor
Fas ligand is bound to the plasma membrane of neighbouring cells
what happens firstly when ligands bind to the death receptor son cells?
the receptor undergoes a conformational change and oligomerize in order to transduce the signal
the conformational change exposes the death domains on the cytoplamsmic tail
this enables intracellular adapter proteins such as FADD and TRADD to bind to their death domains.
where are death domains located on the death receptor?
cytoplasmic tail
when the death domains are exposed which proteins can then bind to these domains?
FADD and TRADD
what does FADD and TRADD stand for
Fas associated death domain protein
TNF Receptor associated death domain protein
what do these FADD and TRADD proteins do when they bind to the death domain on the cytoplasmic tail on the recepot?
transduce the death signal from the receptor to the caspases.
they recruit procaspase 8 which when in close proximity of other procaspase 8 will become activated by self cleavage
how do procaspase 8 become activated once recruited to the death domains by TRADD and FADD?
when they come in close proximity of each other they activate by self cleavage
what is this combination of death ligands, receptor adaptors (FADD and TRADD) and imitator caspases called?
death inducing signalling complex or DISC
once caspase 8 is produced what happens?
they activate other procaspases which are called executioner caspaces
what numbers are the caspases known as executioner caspases?
3,6,7
what does this whole extrinsic pathway result in once caspases 3,6 and 7 are produced by caspase 8 ?
proteolysis of target proteins