Apoptosis

Question 0

Apoptotic protein: normally?

Answer 0

BH3 only family: sequestered to cytosol proteins

Bcl-Bax/Bak: inactivates Bax/Bak

Question 1

3 subgroups of apoptotic proteins? anti or pro-apoptotic?

Answer 1

• 4 domain: anti-apoptotic (Bcl)
• 3 domain: pro-apoptotic (Bax, Bak)
• 1 domain: pro-apoptotic (BH3 only family, Bid)

Question 2

Caspases types?

Answer 2

Apoptosis

1. Initiators- 8,9
2. Executioner/effector- 3, 6, 7

Question 3

Apoptosis: intrinsic pathway

Answer 3

1. Bid released from cytoplasmic proteins
2. Bid binds Bcl –> release of Bax/Bak
3. Bax/Bak forms pore –> cyt-c and Smac/DIABLO release
4. 7 Cyt-C + 7Apaf-1 + procaspase9 –> apoptosome
5. caspase 9 activates caspase 3,6,7 –> apoptosis

Question 4

IAP?

Answer 4

Apoptosis inhibitor
part of intrinsic pathway
inhibits caspase 3,6,7
Smac/DIABLO inhibits IAP

Question 5

Apoptosis: extrinsic pathway?

Answer 5

1. ligand binds death receptor
2. death receptor recruits/binds FADD –> DISC complex
3. DED of DISC complex recruits procaspase8
4. caspase 8 will activate caspase3,6,7 (also activates Bid)

Question 6

Apoptosis: granzyme-b

-also: what is it? where does it come from?

Answer 6

serine protease
released by CD8+ T cells and NK cells
released with perforin (helps enter cell)
granzyme b activates caspase 3,8

Question 7

Apoptosis: p53

Answer 7

• upregulated with stress

- p53 upregulates Bid and DR; helps Bax/Bak activity

Question 8

Apoptosis: caspase indpendent pathway?

Answer 8

AIF (released from mitochondria w cyt-c and DIABLO)

will go directly to nucleus and fragment DNA