Lecture 30 - Apoptosis

Question 1

What is the key difference between apoptosis and necrosis?

L30 S3

Answer 1

Apoptosis:
-cell contents do not leak

Necrosis:
-cell contents spill out

-apoptosis minimizes the spread of damage/inflammation

Question 2

What are the characteristics of apoptotic cell death?

L30 S6

Answer 2

• shrinkage of cell volume
• loss of adhesion to neighboring cells
• DNA fragmentation
• cytoskeleton collapses
• engulfment of dying cell by macrophages

Question 3

What is a caspase?

L30 S9

Answer 3

(C)ystine (ASP)artyl specific prote(ASE)

• proteases that play a key role in apoptosis
• cysteine in active site
• target proteins and cleaves them at aspartic amino acid

Question 4

How are procaspases converted to caspases?

L30 S10

Answer 4

• cleavage into a large and small subunit which then form heterodimers
• activation of procaspases can be performed by caspases (positive feedback)

Question 5

What are the two major classes of caspases and what do they do?

L30 S11

Answer 5

Initiator caspases:

• initiate apoptosis
• caspase 8/10 and 9
• activates other caspases

Executioner caspases:

• destroys other proteins
• caspase 3

Question 6

What is the extrinsic pathway for apoptosis?

L30 S14-18

Answer 6

• Fas (ligand) trimers bind Fas death receptor trimers
• FADD (Fas associated death domain) and procaspase-8 or 10 bind in trimers to activated receptors; this forms DISC (death induced signal complex)
• procaspase-8 or 10 is activated
• executioner caspases (caspase-3) are activated

-mitochondrial independent

Question 7

What factors inhibit the extrinsic pathway of apoptosis and how?

L30 S19-20

Answer 7

Decoy receptors:
-bind Fas but lack death domain and therefore don’t initiate apoptosis

FLIP:
-competitively binds with procaspase-8 and 10 but has no proteolytic domain

Question 8

What is the intrinsic pathway for apoptosis?

L30 S21-22

Answer 8

• cytochrome C is released from the mitochondria through BH123 complex
• cytochrome C binds Apaf1 (apoptotic protease activating factor-1) which forms an apoptosome
• apoptosome activates caspase-9
• caspase-9 activates executioner caspases (caspase-3)

Question 9

What is the Bcl2 family of proteins and what types are present and how do they function?

L30 S23-24

Answer 9

BH123:

• aggregate in outer mitochondrial membrane to release cytochrome C
• pro-apoptotic

Bcl2:

• prevents aggregation of BH123 proteins
• cytosolic
• anti-apoptotic

BH3:

• inhibits Bcl2
• cytosolic
• pro-apoptotic

Question 10

What are IAPs and anti-IAPs?

L30 S31-34

Answer 10

(I)nhibitors of (AP)optosis

IAPs:

• bind and inhibit caspases
• can ubiquinate and target for proteolysis
• anti-apoptotic

anti-IAPs:

• inhibit IAPs allowing executioner caspases to be activated
• released when apoptotic stimulus is present
• pro-apoptotic

Question 11

Over inhibition of apoptosis can result in cancer.

L30 S36-37

Answer 11

It’s just a thing you need to remember.