White: Apoptosis

Question 1

Apoptosis definition

Answer 1

A routine controlled cell death that minimizes spread of damage and/or inflammation

Question 2

Phenotype of apoptosis

Answer 2

Overall shrinkage in volume of cell and nucleus
Loss of adhesion to neighboring cells
Formation of blebs on surface
DNA fragmentation
Cytoskeleton collapses
Nuclear envelope disassembles
Rapid engulfment of dying cell by phagocytosis

Question 3

Procaspases

Answer 3

Caspases synthesized first as an inactive precursor

Becomes activated by protease cleavage

Question 4

Initiator caspase

Answer 4

Initiates apoptosis

Question 5

Executioner caspase

Answer 5

Destroys actual targets, executes apoptosis

Question 6

Extrinsic apoptosis pathway steps

Answer 6

Fas binds to Fas death receptor
FADD adaptor & procaspase-8 with death effector domain recruited
Bring death domains together forming DISC
Activates caspase-8 or 10
Activates downstream executioner caspase-3

Question 7

Decoy receptors

Answer 7

Have ligand binding domain but no death domain, can bind death ligand but does not activate apoptosis

Question 8

FLIP

Answer 8

Protein resembling initiator procaspase with no proteolytic domain
Competitive inhibitor against procaspase-8/10–prevents apoptosis
Decoy proteins and FLIP act as sponges

Question 9

Key event in intrinsic pathway

Answer 9

Translocation of cytochrome c from the intermediate space of mitochondria to cytosol, binds adaptor protein to activate procaspases

Question 10

Intrinsic pathway steps

Answer 10

Cytochrome C released from mitochondria and binds Apaf1
Apaf1 forms apoptosome which activates caspase-9
Caspase-9 activates downstream executioner caspase-3

Question 11

Bcl2 family function

Answer 11

Controls release of cytochrome C into cytosol

Can have proapoptotic or anti-apoptotic function, which promote or block the release of cytochrome C, respectively.

Question 12

Anti-apoptotic Bcl2 family members include and their function/location

Answer 12

Bcl2 and Bcl-XL
Located on cytosolic surface of outer mitochondrial membrane
Prevent apoptosis by binding to pro-apoptotic proteins and prevent aggregation into active form

Question 13

Pro-apoptotic Bcl2 family members inclue

Answer 13

BH123 and BH3-only

Question 14

BH123 proteins

Answer 14

Pro-apoptotic
BH123 proteins become activated, form aggregation in mitochondrial outer membrane and induce release of cytochrome C– then apoptosome formed by binding to Apaf1

Question 15

BH3 only protein

Answer 15

Pro-apoptotic
Active BH3-only protein is cytosolic
Translocates to mitochondria after apoptotic signal activates it
Inhibits anti-apoptotic Bcl2 protein from inhibiting aggregation of BH123 which allows release of cytochrome C

Question 16

IAPs

Answer 16

Inhibitors of apoptosis
Bind and inhibit caspases
Some IAPs add ubiquitin to caspases

Question 17

Anti-IAPs

Answer 17

Pro-apoptotic

Apoptotic stimuli causes release of Anti-IAPs from mitochondria to block activity of IAPs