8: Necrosis and Apoptosis 2 Flashcards
PCD: essential for? examples?
development and maintenance of multicellular organisms: formation of fingers/toes, formation of functional synapses (since surplus cells have to be eliminated)
PCD: required to destroy cells that? 4 ex?
cells that represent a threat to the integrity of the organism: cells infected with viruses. cells of immune system. cells with DNA damage. cancer cells.
3 forms of PCD? when do they occur?
type 1 = nuclear/apoptotic. 2 = autophagic. 3 = cytoplasmic. various forms occur in specific nuclei and at specific developmental stages. can also be induced by insults like DNA damage, misfolded protein accumulation.
death in the NS may trigger?
stem cell proliferation and survival = cell death pathways can be potential points of entry for therapeutics of neurodegen diseases
best characterized form of PCD = ? 3 pathways?
Type 1, aka apoptosis. intrinsic, extrinsic, caspase independent.
intrinsic pathway: aka? conservation? propensity for cell to undergo apoptosis determined by?
mitochondrial pathway, largely conserved from worms to mammals. balance between the anti and pro apotoic members of the Bcl-2 family of proteins
intrinsic pathway: gatekeepers of apoptosis process? what executes the program?
members of the B-cell leukemia/lymphoma 2 family of proteins. caspases, aka cysteine aspartate proteases execute the program
BCl-2 family: anti apoptotic? what domain?
Bcl-2 and Bcl XL. have the B4 domain.
bcl2 family: 3 types of pro-apoptoic proteins and what domains they have?
multi domain proteins BH 1 = 3. BH3 only. BH3 only de-repressors.
multi domain bcl2 proteins: 2 examples? have?
BAX and BAK. have Bcl2 homology domains 1 -3
BH3 only proteins: example? what does it do?
BIM: activates BAX and BAK, likely participate in mitochondrial pore formation
BH3 only de-repressors: 3 examples? action?
PUMA, NOXA, BAD. sequester anti-apoptotic Bcl2 and BclXL proteins and other proteins with BH1-4 domains which allows BH1-3 proteins to permealize the mitoch. membrane
BH4 domain: who has it?
only the anti-apoptotic members of the bcl2 family have it
formation of mitochondrial pore causes release of 2 things?
pro-apoptotic proteins: cytochrome C and SMAC/DIABLO released into cytoplasm
what does cytochorme C do? then?
induces heptamerization of cytosolic protein APAF-1 (apoptosis activating factor), which then binds caspase 9 = formation of apoptosome.
formation of apoptosome results in (3)?
activation and cleavage of effector caspases 3 and 7, then you get digestion of structural proteins and chromosomal DNA, then phagocytosis of cell.
activated effector caspases can be held in check by? ex? but what inhibits those?
IAPs = inhibitors of apoptosis, for example XIAP. SMAC/diable can inhibit IAPs and thus apoptosis can proceed.
extrinsic pathway: aka? 5 examples of ligands?
death receptor pathway: FasL/FasR. TNFa/TNFR1, Apo3L and 2L onto DR3, 4, 5.
basic events in extrinsic pathway
pro-apoptotic ligand binds death receptor. caspase 8 activation, followed by caspase 3, 6, 7, and apoptosis
Fas and TNF receptors are?
integral membrane proteins, with receptor domains exposed at surface of cell
Fas receptor: binds what ligand? causes?
trimeric fas ligand = FasL. causes recruitment of FADD through Fas’s death domain.
what does FADD do?
recruits capspase 8 through FADD’s death effector domain. activates 8, which then activates effector caspases 3 and 7.
how can extrinsic pathway interact with intrinsic pathway?
caspase 8 cleavage of BID to make tBID.. which then triggers intrinsic pathway
