Apoptosis regulation Flashcards
direct inducers of apoptosis: ???
Engagement of cell surface receptors
indirect inducers of apoptosis include ???
Withdrawal of growth (or survival)
factors, DNA damage, An ever increasing list of chemical
agents
??? embryos helped determine mechanisms for the regulation of apoptosis
C. elegans
CED-3, CED-4, and CED-9 are knock out mutants identified as being critical in the control of ???
control of C. elagans apoptosis
CED-??? homologue identified as a caspase
CED-3
CED-4 or CED-9 (?) homologue identified as Apaf1 (apoptotic peptidase activating factor 1
CED-4
CED-9 homologue identified as ???
Bcl-2
Caspase-1, -4, -5, -13, -14 (and caspase-11, -12 in mice) are involved in inflammation or apoptosis?
inflammation
Caspases involved in apoptosis:
Initiator caspases: caspase-2, -8, -9, -10 (interact with executioner caspases)
Executioner (aka effector) caspases: ? ? ? (initiate cell death)
3, -6, -7
??? initially exist as inactive procaspases (zymogens). Proteolytic cleavage = activation. Two fragments combine to form an active ???
Caspases
??? cleave and activate downstream executioner (effector) procaspases
Initiator caspases
caspases target:
- Protein kinases (Includes focal adhesion kinase)
- Laminins (Comprise inner lining of nuclear envelope)
- Cytoskeleton proteins (Include intermediate filaments, actin, tubulin, gelsolin)
- ??? (An endonuclease, once activated it translocates to the nucleus to cleave DNA)
Caspase-activated Dnase (CAD)
Bcl-2 or caspases (?) resides in outer membrane of mitochondria to maintain its low permeability
Bcl-2
EXTRINSIC or INTRINSIC (?) pathway of apoptosis:
Activated by external stimuli, involves formation of death-inducing signalling complex (DISC) downstream of cell surface receptor activation
e.g. FasL/Fas receptor, TNF/TNF receptor
extrinsic
EXTRINSIC or INTRINSIC (?) pathway of apoptosis: Activated by internal stimuli. Involves release of cytochrome c from mitochondria and formation of apoptosome
intrinsic
fas protein ligand binds to fas receptor (CD95), receptor recruits adaptor proteins FADD via death domains in protein. Adaptor protein recruits initiator pro-casoase to from DISC, is activated, activates executioner caspases = apoptosis. This is an example of intrinsic or extrinsic apoptosis pathway?
extrinsic
- ligand such as TNF binds to its receptor
- receptor recruits ??? via death domains present in proteins.
- adaptor protein recruits pro-caspase, activating it
- activated caspase recruits executioner caspases = apoptosis
(EXTRINSIC pathway)
adaptor protein TRADD
intrinsic pathway step 1:
Pro-apoptotic Bcl-2 protein (e.g. Bad, Bax) is inserted into outer mitochondrial membrane to form pores and cause ??? release
cytochrome C
which are the pro-apototic Bcl-2 proteins?
Bad, Bax
intrinsic pathway step 2:
cytochrome C and Apaf1 form a complex. 7 of these complexes combine to form apoptosome which activates ???
activates pro-caspase-9
intrinsic pathway step 3:
Active caspase-9 cleaves and activates ???, leading to apoptosis
executioner caspases
inhibitors of apoptosis inhibit activated CASPASES and include: XIAP, ??? and ???
Livin, and Survivin
anti-inhibitors of apoptosis proteins inhibit survivin and livin (the inhibitors of apoptosis) to cause apoptosis.
- In Drosophila IAPs include proteins Reaper, Grim, Hid
– In mammals IAPs include ???(DIABLO)
Smac and Omi
Extracellular survival factors can inhibit apoptosis. this includes:
1. increased production of ??? which are anti-apoptotic
2. Inactivation of pro-apoptotic BH3-only Bcl-2 proteins
3. incativation of anti-inhibitors of apoptosis such as ???
Bcl-2 and Bcl-X proteins
reaper, grim, smac, omi
