White Lecture 5 "Apoptosis"

Question 1

What are the two forms of cell death?

Answer 1

Apoptosis and necrosis

Question 2

Define necrosis

Answer 2

accidental cell death
dirty way of dying

when it dies, the cell contents leak out. yuck

Question 3

Define apoptosis

Answer 3

routine controlled cell death that minimizes spread of damage and or inflammation

cell death under physiological conditions
clean way of dying
cell programmed death

Question 4

What happens to cells when they are no longer needed?

Answer 4

They die

Question 5

True or false: apoptosis is not important in development of mature forms

Answer 5

FALSE: They are important in development of mature forms

Question 6

Describe the “phenotype” of apoptosis

Answer 6

1. overall shrinkage in volume of cell and its nucleus
2. loss of adhesion to neighboring cells
3. formation of blebs on surface
4. DNA fragmentation
5. Cytoskeleton collapses
6. nuclear envelope dissembles
7. rapid engulfment of dying cell by phagocytosis

Question 7

Why is apoptosis important in the cell?

Answer 7

Can get rid or any abnormal, non-functional, or dangerous cells

eliminate lymphocytes after destroying microbes

keep liver the right size

DNA damaged cells

Question 8

What is the marker of apoptosis?

Answer 8

cytochrome c that is released from mitochondria

Question 9

What is in charge of cleaving DNA into a ladder of fragments in distinctive sizes?
Where do these cleavages occur?

Answer 9

endonuclease

They occur in the linker regions of the nucleosomes

Question 10

Define caspases

Answer 10

cysteine aspartyl specific protease

proteases that mediate apoptosis; targets the proteins and cleaves them in their sequence where an aspartic amino acid occurs

Question 11

Describe procaspases

Answer 11

Inactive precursors of caspases

activated by protease cleavage

Question 12

Describe the activation of caspases

Answer 12

cleaved at specific sites to form large and small subunits which forms a heterodimer then caspases activate them

Question 13

What are the 2 major classes of caspase?

Answer 13

Initiator and Executioner

Question 14

Define initiator caspase

Answer 14

initiates apoptosis

Question 15

Define executioner caspases

Answer 15

destroys actual targets and executes apoptosis

Question 16

Where do the caspases cleave, target, and what do they attack?

Answer 16

The cleave downstream proteins and inactive endonucleases

Target cytoskeleton

attack cell adhesion proteins

Question 17

True or false: The caspase cascade it irreversible

Answer 17

TRUE

Question 18

What are the two apoptosis pathways?

Answer 18

internal and external

Question 19

What are the internal and external stimuli?

Answer 19

Internal are the abnormalities or DNA and the external are the removal of the survivial factors and proteins of the tumor necrosis facto family

Question 20

Describe the intrinsic pathway

Answer 20

mitochondrial dependent

cells can activate from inside the cell; responds to injury

translocation of cytochrome c from the intermediate space of the mitochondria

This is released to the cytosol and will bind to the adaptor protein to activate the procaspases

Question 21

Describe what happens when cytochrome c is released from the mitochondria in the intrinsic pathway

Answer 21

1. binds to the procaspase-activating adaptor proteins (Apaf-1)
2. Apaf-1 forms an apoptosome which activates caspase-9
3. caspase-9 activates downstream executioner caspases

Question 22

Which caspase is common to both pathways?

Answer 22

caspase 3

Question 23

Describe the extrinsic pathway

Answer 23

1. Fas binds to the Fas Death receptor
2. FADD adaptor and the procaspase 8 come to the death effector domain
3. trimers are formed that bring the death domains together to from the DISC (death inducing signal complex)
4. activates caspar 8 or 10
5. Activates downstream executioner caspases

Question 24

Define decoy receptors

Answer 24

inhibitory protein that restrain the extrinsic pathway;

have a ligand binding domain but no death domain

Question 25

Define FLIP protein

Answer 25

a protein resembling initiator procaspase with no proteolytic domain

competitive inhibitor against procaspase 8 and 10

prevents apoptosis

Question 26

Describe the Bcl2 family of proteins

Answer 26

regulate the intrinsic pathway

Bcl2 controls the release of cytochrome c

Question 27

What are the two types of the Bcl2 proteins?

Answer 27

antiapoptotic and proapoptotic

Question 28

Define anti-apoptotic

Answer 28

prosurvivial obvs

blocks the release of cytochrome c

has 4 distinctive domains

Question 29

Define pro-apoptotic

Answer 29

promotes the release of cytochrome c

BH123 and BH3 only

Question 30

Describe the BH-123 protein in apoptosis

Answer 30

pro-apoptotic

apoptotic stimulus triggers intrinsic pathway

activated and form aggregation in mitochondrial outer membrane and induce the release of cytochrome c then an apoptsome formed by binding to Apaf1

Question 31

Describe anti-apoptotic Bcl2 proteins

Answer 31

located on the cytosolic of the outer mitochondrial membrane

prevents apoptosis by binding to the pro-apoptotic proteins and prevent aggregation into the active form

Question 32

Describe the BH3-only protein

Answer 32

cytosolic

translocates to the mitochondria after apototic signal activates it

inhibits anti-apoptotic Bcl2 protein from inhibiting aggregation to relate cytochrome c

PROAPOPTOTIC

Question 33

What do IAPs do?

Answer 33

Inhibitors of Apoptosis

bind and inhibit caspases

some IAPs add ubiquitin to caspases to mark them for destruction by proteasome

block apoptosis

help with the auto-activating issue

ANTI_APOPTOTIC

Question 34

What do anti-IAPs do?

Answer 34

released from the mitochondria to block the activity of the IAP’s so that the executioner caspases can be blocked

LIBERATE caspases

Question 35

What happens in the event that there is excess Bcl2?

Answer 35

development of cancer by inhibiting apoptosis;

B cell lymphoma

Question 36

What can occur in the event of excessive apoptosis?

Answer 36

heart attacks and strokes