7. Apoptosis Flashcards
Phosphatidyl serine
Increase of outwards-facing PS in plasma membrane are a indicator of apoptosis as well.
BH3-only proteins
Pro-apoptotic proteins eg. Bad, Bim, Bid, Puma, Noxa.
Caspase 3 cleavage
Catalyzed by caspase 9, facilitated by apoptosome assembly.
Granzyme B
Protease capable of truncating Bid, causing it to inhibit Bcl2 proteins.
BH123
Bax, Bak
Caspase cascade
Initiator caspases cleaves executioner caspases that cleaves cytosolic proteins and nuclear lamins.
Ced-3
Caspase. Cleaves after aspartic acid residues.
Bcl-xl, Bik function regulation
Bcl-xl sequesters Apaf-1 on the mitochondric surface. Bik binds and displaces Apaf-1, releasing it to form the apoptosome.
Bcl2 regulation
Bax, Bak (BH123 induces intrinsic apoptosis. Are inhibited by Bcl-2 proteins. BH3-only proteins inhibits Bcl2 proteins.
Asaptor proteins
Mediates dimerization of initiator caspases, which facilitates cleavage in trans of the inactive monomers.
Binding of cyt c to Apaf-1 results in…
ADP exchange for dATP and following oligomerization.
CARD domains
Dimerization domains found on eg. Apaf-1 and caspase 9.
What does cell do without trophic factors?
Undergo apoptosis.
p53 regulation of Bax and Bak function
Presumes to help Bax and Bak into an active conformation. Induces expression of Fas and Bax. (and IFGBP-3)
Death domain
Oligomerization domain between Fas death receptor, FADD adaptor protein and procaspase 8 or 10.
Apoptosome consists of
Apaf-1, Cyt C and caspase 9
BH3 only
Bim, Bik, Bid, Puma, Noxa, Bad
Bcl-2 proteins
Anti-apoptotic proteins. Eg. Bcl2, Bcl-Xl. Have BH4, 3, 2 and 1.
Bax, Bak function
Bax and Bak make up the channel through which Cyt C is releases. Gets sequestered and inhibited by Bax or Bak.
Procaspase activation
Caspases are activated by cleavage of the inactive procaspase into the active caspase.
Initiator caspases
Caspase 8,9
Bcl2 proteins
Family consist of Bcl2, BH123 and BH3-only proteins.
Apoptosis characteristics
Individual cells, decreased cell volume, condensed chromatin. No inflammation
Necrosis characteristics
Multiple cells, increased cell volume, inflammatory resonse.
TUNEL
dUTP nick end labeling: labels bare DNA ends - sign of apoptosis
Two major types of cell death
Apoptosis and necrosis
Diablo/SMAC
Released from mitochondrion with Cyt C. Inhibits IAPs
Bcl2 proteins (subgroup)
Bcl2, Bcl-Xl
IAPs
Inhibitor of apoptosis proteins. Presumely binds active caspase as eg. XIAP, blocking caspase function
Cyt C release
Release of Cyt C from mitochondria are a sign of apoptosis.
3 strategies to avoid apoptosis:
Increased production of Bcl2 protein, inactivation of BH3-only Bcl2 proteins by active Akt, inactivation of anti-IAPs with MAPK-mediated phosphorylation
Fas ligand
Binds Fas death receptor. Induces apoptosis in target cell.
DNA fragmentation
In apoptosis, DNA fragments, creating af DNA ladder cause of fragmenting of linker regions between nucleosomes.
Executioner caspases
Caspase 3,6,7
Extrinsic pathway activation
Through cell death receptors. Binding induces DISC formation in which procaspase 8 is cleaved into caspase 8, initiating apoptosis.
FADD
Fas-associated protein with death domain.
Two ways Death receptor can induce apoptosis
Direct cleavage of procaspase 3 by caspase 8 or truncation of Bid, causing release of Cyt C.
Roles of apoptosis
Morphogenesis, synaptogenesis, tissue turnover, removal of stressed cells
BH123
Pro-apoptotic proteins. Eg. Bax, Bak.
