Apoptosis

Question 1

What are caspases?

Answer 1

A family of enzymes (proteases) that hydrolyze specific bonds in proteins. They contribute to cell death by inactivation of important proteins.

Question 2

What is the caspase cascade?

Answer 2

Procaspase (8, 9, 10)

Caspase (8, 9, 10)

Caspase (3, 6, 7)

Cleavage of cellular proteins

Question 3

How is procaspase activated?

Answer 3

Autocatalytic upon binding to an adaptor anchored at the PM

Question 4

What are characteristics of an apoptotic cell?

Answer 4

Changes in protein content of PM causes PM to bleb

Activated endonucleases (caspase-activated DNase): Nuclear DNA fragments

Degradation of and changes in cytoskeletal proteins change cell shape

Question 5

What are 2 major death ligands? What is an example of a receptor?

Answer 5

TNF-alpha and FAS ligand (FASL)

CD95

Question 6

What do “death ligands” bind to and what results?

Answer 6

Bind to the cell surface receptor which recruits an intracellular adaptor protein called FADD which recruits procaspase 8

Question 7

What causes apoptosis in the mitochondria?

Answer 7

Translocation of cytochrome C from the inner membrane space to the cytosol via pores.

Question 8

What happens to cytochrome C once it reaches the cytosol?

Answer 8

It binds apoptotic protease-activating factor 1 (Apaf-1) and procaspase-9 to form an apoptosome (complex).

Question 9

What does the formation of an apoptosome cause?

Answer 9

Autocatalytic activation of procaspase-9 to caspase-9 and activation of the cascade

Question 10

What regulates the release of cytochrome C from the mitochondria?

Answer 10

Pro-apoptotic factors:
Bax and Bak

Anti-apoptotic factors:
Bcl-2 and Bcl-2 like proteins.

Question 11

In the cytochrome-c, caspase pathway, how do pro-apoptotic factors promote apoptosis?

Answer 11

Bax and Bak make up the pores through which cytochrome C pass and are helped by facilitators Bid, Bad, and Nova.

Question 12

Describe the Smac/DIABLO pathway

Answer 12

XIAP inhibits caspases (apoptosis)

Smac/DIABLO protein inhibits XIAP, allowing the caspase cascade to proceed

Question 13

p53 has a(n) _______ effect on apoptosis

Answer 13

activating

Question 14

Upon exposure to DNA-damaging agents, p53 is _______.

Answer 14

Upregulated

Question 15

How does p53 induce apoptosis (in relation to the cytochrome c pathway)?

Answer 15

Increases the transcription of pro-apoptotic genes such as Bax and Nova

Question 16

MAPK has a(n) ______ effect on apoptosis

Answer 16

Inhibitory

Question 17

What activates MAPK?

Answer 17

Growth factor signals
UV light
Radiation

Question 18

What is Raf and what does it do? (Relate this to the RTK signaling pathway)

Answer 18

Raf is a MAPK

It phosphorylates Bad, leading to its dissociation from the mito membrane and inhibition of apoptosis