Apoptosis

Question 1

What occurs during apoptosis?

Answer 1

Irreversible once started

Chromatin and nucleus fragments

Cytoskeleton breaks up

Cell shrinks and breaks up into membrane-enclosed fragments

Question 2

What is the role of phosphatidylserine in apoptosis?

Answer 2

Flipped to outer leaflet during apoptosis

Recognized by macrophages for phagocytosis

Question 3

What are caspases?

Answer 3

Protease that is responsible for cleaving many different cell proteins during apoptosis

Question 4

What are the two types of capsases?

Answer 4

Initiator and executioner capsases

Question 5

What are the targets of capsases?

Answer 5

ICAD

Nuclear lamins

Cytoskeletal proteins

Golgi matrix proteins

Scramblase

Question 6

What are the two main pathways of apoptosis/

Answer 6

Intrinsic/Stress

Extrinsic/Death receptors

Question 7

What are two antiapoptotic proteins?

Answer 7

Bcl-2

Bcl-xL

Question 8

What is the function of Bad and Bid?

Answer 8

Proapoptotic proteins that block Bcl-2 and Bcl-xL interaction with pro-apoptotic proteins

Question 9

What is the function of Bak and Bax?

Answer 9

Proapoptotic proteins that translocate to the mitochondria where they are thought to insert in membrane and disrupt its integrity, allowing cytochrome c release

Question 10

How is the mitochondrial/intrinsic pathway activated?

Answer 10

DNA damage or mitchondrial damage causes Apaf-1 and cytochrome c release from the mitochondria to the cytoplasm

Question 11

What is an apoptosome?

Answer 11

Multi subunit complex formed by Apaf-1, cytochrome c, and ATP

Caspase-9 binds to this complex and is activated by autocleavage

Question 12

What is the function of caspase 9?

Answer 12

Proteolytic activation of Caspase-3 and Caspase-7

Question 13

How is the extrinsic pathway activated?

Answer 13

When membrane bound FasL on the surface of one cell binds to Fas receptor on surface of another cell

Question 14

What occurs when ligand binds to Fas receptor?

Answer 14

Fas trimerizes and binds to its adaptor FADD, via death domains at the C-terminal of both proteins

Question 15

What is the function of FADD?

Answer 15

Once it binds to Fas, it binds capsase-8 via death effector domains at its N-terminus

Question 16

What happens when capsase-8 binds to FADD?

Answer 16

Autocleavage and activation of C-8, diffuses to cytoplasm and activates C-3

Question 17

How does Capsase-8 combine the two pathways?

Answer 17

Cleaves Bid, which translocates to the mitochondria and disrupts the membrane.

This causes the release of cytochrome c

Question 18

What are five ways apoptosis is regulated?

Answer 18

Positive feedback and amplification

Buffers/dampeners

FLIPs

Decoy receptors

p53

Question 19

What is the function of inhibitors-of-apoptosis proteins (IAPs)?

Answer 19

bind to procaspases and caspases

Question 20

What is the function of Smac/Diablo?

Answer 20

Inhibits IAPs

Question 21

What is the function of FLIPs?

Answer 21

compete with caspase-8 for binding to FADD

Lacks catalytic residues

Question 22

What are decoy receptors?

Answer 22

Bind to apoptosis-inducing ligand, but cannot transduce apoptotic signal

Question 23

What is the role of p53?

Answer 23

Tumpor suppressor protein

Activated via DNa damage

Initiates transcription of pro-apoptotic genes PUMA and Noxa

Question 24

What types of diseases are caused by excessive apoptosis?

Answer 24

Neurodegenerative

Immune deficieny

Cardiovascular

Emphysema

AIDS

Question 25

What types of diseases occur with too little apoptosis?

Answer 25

Cancer

Autoimmune disease

Question 26

What are two ways cancer cells escape apoptosis?

Answer 26

IAPs expression increased

Anti-apoptotic Bcl-2 protein levels increased

Question 27

What are some apoptotic cancer treatment?

Answer 27

BH3 mimetics

XIAP antagonists

FasL mimetics and Fas activators