Apoptosis

Question 1

Name the 3 types of cell death

Answer 1

Apoptosis
Necrosis
Autophagy

Question 2

Describe the 3 types of cell death

Answer 2

Apoptosis
= Regulated cell death
= No spillage

Necrosis
= Entire cell burst
= Contents spill out
= Can have an inflammatory reaction

Autophagy
= Self-eating
= Acidified container in cells swell

Question 3

What processes in the body is significantly apoptosis involved in?

Answer 3

Oocyte development 
Immune system activation
Disease:
-> cancer (too little)
-> Alzheimer's (too much)

Question 4

Describe the process of apoptosis

Answer 4

1) DNA fragmentation
   Chromatin condensation
   Membrane blebbing (outgrowths)
   Cell shrinkage
2) Fragmentation
    Disassembly into apoptotic bodies
3) Engulfment by neighbouring cells

Question 5

What are the neighbouring cells that engulf dead cells that were killed by apoptosis?

Answer 5

Phagocytes

Question 6

What are the triggers of apoptosis?

Answer 6

Extrinsic:
= Death receptors (e.g. TNF (tumour necrosis factor))
= Growth factor withdrawal (EPGF)
= Loss of contact w/ surroundings

Intrinsic:
= Irreparable internal damage (DNA damage)
= Conflicting signals for cell division

Question 7

What are the regulators of apoptosis?

Answer 7

p53

Bcl-2 family

Question 8

What are the executioners of apoptosis?

Answer 8

Apaf-1

Caspases

Question 9

What does caspases stand for?

Answer 9

Cysteinyl aspartate specific proteases

Question 10

Name 4 key features of caspases

Answer 10

1) Highly specific
2) Recognition of at least 4 amino acids N-terminal to the cleavage site
3) Variable N domain regulates activation
4) All domains derived from inactive precursor by cleavage specific sites

Question 11

How do caspases disassemble a cell?

Answer 11

Inhibition of anti-apoptotic proteins (bcl-2)

Breakdown cell structures (e.g. nuclear lamins -> DNA breakdown)

Question 12

What initiates + controls intrinsic signalling pathways of apoptosis?

Answer 12

Initiated by conflicting cell division/irreparable DNA damage signals

Controlled by intracellular Bcl-2 protein family at mito.

Question 13

What initiates + mediates extrinsic signalling pathways for apoptosis?

Answer 13

Initiated by growth factor withdrawal, radiation, chemicals …

Mediated by members of TNF receptor

Question 14

What is FADD?

Answer 14

Fast activated death domain
Intracellular domains of TRAIL receptors
Activates initiator caspase 8

Question 15

What are IAPs?

Answer 15

Inhibitors of apoptosis proteins

Work at multiple sites of signalling pathway

Question 16

Describe an extrinsic signalling pathway of apoptosis (hint: TRAIL)

Answer 16

1) TRAIL ligand binds to a TRAIL receptor (TRAILR1 or TRAILR2) -> trimerisation of receptors
2) FADD (domains) brought close together -> activates cascade of signalling molecules (one being caspase 8)
3) Activated initiator caspase 8 activates executioner caspase 3
4) Caspase 3 targets intracellular components -> apoptosis

Question 17

Describe a internal signalling pathway of apoptosis

Answer 17

1) Active caspase 8 activates/truncates BID (protein) to form active tBID (pro-apoptotic)
2) tBID inhibits BCL2 (on mito.) + BCL2 inhibits BAX + BAK (on mito.)
3) tBID also activates BAX + BAK (pro-apoptotic)
4) Makes mito. membrane more porous (MOMP = mitochondrial outer membrane permeabilisation)
5) Molecules (e.g. cytochrome c + DIABLO) leak out of mito.
6a) Cytochrome c activates APAF (protein) -> forms apoptosome -> activates caspase 9 -> activates caspase 3 -> apoptosis
6b) DIABLO inhibits the IAPs -> activates caspase 9 -> activates caspase 3 -> apoptosis

Question 18

BCL-2 protein family includes what protein?

Answer 18

Anti-apoptotic:
= BCL-2
= BCL-B
= BAL-X1 …

Pro-apoptotic:
= BAX + BAK

Pro-apoptotic initiators (BH3 only):
BID

Question 19

How do cancer cells avoid apoptosis?

Answer 19

Over-expression of anti-apoptotic proteins (e.g. BCL-2)

and/or

Over-expression of pro-apoptotic protein inhibitors/mutations in pro-apoptotic genes (e.g. BAX + BAK)

Question 20

Not all tumour cells survive (survival of the nastiest)

What types of cell death are involved in cancer/tumours?

Answer 20

Apoptosis

Autophagy