Chapter 7

Question 1

What molecular flag that apoptotic cells release is recognized by neighboring cells

Answer 1

Phosphatidyl serine

Question 2

what is the function of apoptosis?

Answer 2

1. Developmental morphogenesis
2. Controls cell numbers
3. Removes damaged cells
4. Negative and positive selection of lymphocytes

Question 3

What are the two major apoptotic pathways?

Answer 3

1. Intrinsic -> the mitochondrial pathway, mediated by DNA damage or more intrinsic factors
2. Extrinsic -> The pathwat mediated by a death receptors like TNFR, TRAIL and FAS

Question 4

What is the enzyme that prevents formation of caspase 8 from procaspase 8?

Answer 4

c-Flip

Question 5

What enzymes does Bcl2 inhibit?

Answer 5

Bcl2 inhibits the activity of Bak/Bax enzymes

Question 6

What is the role of XIAP?

Answer 6

It inhibits Caspase 9 and Caspase 3

Question 7

Are BH3 enzymes apoptotic or anti-apoptotic?

Answer 7

BH3 enzymes are apoptotic. They are induced by p53 activity

Question 8

What is the mechanism of action of c-flip?

Answer 8

c-Flip binds to the death domains of death receptors (TNFR and FASR), hereby preventing the activation of caspase 8

Question 9

Which proteins form the apoptosome heptamer?

Answer 9

Cytochrome C, Apaf-1 and Procaspase 9 -> Caspase 9 gets activated from the heptamer

Question 10

Which protein makes a hole in the mitochondrial membrane?

Answer 10

Bax protein

Question 11

Which protein activates Bax after the cell suffers cell stress?

Answer 11

BH3-only protein Bid

Question 12

What is BH3?

Answer 12

BH3 is a protein domain on the Bcl-2 proteins. Proteins that contain only a BH3 are usually pro-apoptotic

Question 13

Name a transcription-independent way in which p53 induces apoptosis

Answer 13

p53 can activate Bax in the cytoplasm and subsequent release of Cytochrome C.

Question 14

Name a transcription-dependent way in which p53 induces apoptosis

Answer 14

p53 induces gene transcription of proteins that apre pro apoptotic. Proteins like death receptors, pro-apoptotic Bak and Bax, repress the expression of Bcl-2

Question 15

In which ways do cancer cells prevent apoptosis?

Answer 15

1. Mutations in genes regulating apoptosis
2. Inhibition of pro-apoptotic genes
3. Up-regulation of anti-apoptotic genes

Question 16

Name a few mutations in the intrinsic pathway and the cancers they can cause

Answer 16

1. p53 mutation - most solid tumors
2. Apaf-1 epigenetic inactivation, no apoptosome can be formed - metastatic melanoma
3. Bcl-2 amplification. no apoptosis can occur
4. Bax mutation - no Bax activity
5. XIAP overexpression - inhibition of caspases

Question 17

Name a few mutations of the extrinsic pathway

Answer 17

1. Fas receptor mutation

2. Caspase mutations

Question 18

How can Bcl-2 be therapeutically deactivated?

Answer 18

1. Inhibit gene transcription
2. Break down of Bcl-2 mRNA
3. Inhibition with small-molecule inhibitors
4. Inhibition with endogenous antagonisys