Apoptosis Flashcards
How was BCL-2 identified?
As part of the t(14;18) chromosomal found in 85% of human follicular B cell lymphomas.
Bcl2 gene put next to a very strong promoter normally controlling ab production in B cells.
Outline the Fas mediated pathway.
Fas l binds Fas - trimer forms.
Trimer binds DEATH domains of FADD adaptor.
FADD associated with procaspase 8 via dimerisation of DEATH EFFECTOR domain.
DISC forms –> autocatalytic activation of procaspase 8.
How does XIAP function as an inhibitor?
BIR3 domain interacts with procaspase9
Preventing dimerisation and activation of caspase9
Describe the intrinsic GF withdrawal pathway.
No PI3K activity.
BAD remains unphosphorylated and can’t bind 14-3-3
Not sequestered away from mitochondria.
Binds BCL-2 preventing apoptotic inhibition.
How are BH3 proteins transcriptionally modulated?
P53 activates expression of Bax and Bid and PUMA and NOXA
Represses expression of BCL-2 and BCL-xl
How are BH3 only proteins post-translationally modified?
Bad sequestered in cytoplasm by 14-3-3
Bim by dynein LC linked to microtubules.
Bid by caspase 8.
What post translational modifications can caspases undergo?
Phosphorylation of caspase-9 by AKT
s-nitrosylaion of caspase-3
Also undergo transcriptional regulation and compartmentalisation.
How do bacteria induce apoptosis?
Produce apoptosis inducing virulence proteins
E.g chlamydia produces cadd which binds TNF death receptors.
How do viruses get around apoptosis?
Encode anti-apoptotic molecules to avoid immune cell destruction.
E.g adenovirus produces E1B
Baculovirus - p35 is an IAP.
What is the mitochondrial integrity model?
Why does the channel theory not hold?
Proteins of Bcl-2 family are responsible for health and wellbeing of mitochondria. pro-apoptotic molecules destroy integrity either directly or indirectly.
Some Bcl-2 family members can act as ion channels - but pores aren’t large enough to let cytochrome C out.
