Regulation Of Apoptosis

Question 1

Is the plasma membrane intact during apoptosis?

Answer 1

Yes, portions bleb off and lose their symmetry
. Requires ATP
. Cytochrome C remains w/ membrane blebs

Question 2

Phagocytic cell role in apoptosis

Answer 2

. Engulf apoptotic cells
. Bind to phosphatidylserine on membrane surface
. Release cytokines (interleukin-10 and transforming GF B) that inhibit inflammation
. No extensive damage to neighboring cells

Question 3

How long does apoptosis take?

Answer 3

A few hours

Question 4

Reasons for cell to undergo apoptosis

Answer 4

. Cell damaged beyond repair
. Cell innfected w/ virus
. Cells experiencing starvation
. Effects of radiation or toxins

Question 5

P53 role in apoptosis

Answer 5

.p53 binds to p53-responsive element w/in gene promoter of the pro-apoptotic protein Bax

Question 6

Apoptosis in developing tissue

Answer 6

. Cell division and differentiation cause excess of cells that must be removed for normal development
. In vertebrate nervous system over half of nerve cells generated undergo cell death

Question 7

Sonic hedgehog pathway

Answer 7

. Sends anti-apoptotic signal to allow doe cell survival w/ failure to receive signal resulting in apoptosis
. When impaired cells don’t die and have potential for developing malignancy

Question 8

Internal cell death program

Answer 8

. Occurs if there is irreparable damage to cell
. bax protein is induced and allows cytochrome C to be released from mitochondria into the cytoplasm
. Cytochrome C activates Apaf-1 adaptor protein that activates caspase 9 of the caspase proteolytic cascade
. This results in cleavage of cellular proteins and DNA in order to affect cellular suicide
. Large protein complex forms in ATP dependent manner (apoptosome)

Question 9

Death receptors

Answer 9

. Belong to tumor necrosis factor receptor gene superfamily
. Contain homologous cytoplasmic sequence called death domain
. Molecules like FADD, TRADD, or DAXX contain death domains so they interact w/ death receptors and transmit apoptotic signals through caspase 8 or 10 activation

Question 10

Fas

Answer 10

. Death receptor

. Initiate apoptosis when engaged by Fas ligand

Question 11

TNF-R1

Answer 11

. Involved in death signaling

. Death inducing capability weak compared to Fas

Question 12

Caspase

Answer 12

. Family of proteases of cysteine protease class (Cys w/in catalytic site)
. Major effectors of apoptotic death
. Synthesized as zymogen
. Classification based on function

Question 13

Caspase 1

Answer 13

Cytokines maturation

Question 14

Caspase 2, 8, 9, and 10 function

Answer 14

Initiator caspase
. Possess regions or domains (caspase recruitment domain in 2/9 and death effector domain in 8/10)
. Enable protease to interact w/ molecules that regulates their activity
. Cleave inactive proenzyme forms of effector caspases resulting in this activation

Question 15

Caspases 3, 6, and 7 function

Answer 15

Effector caspases
. Executioner caspases
. Proteolytically cleave protein substrates w/ the cell causing apoptotic death

Question 16

Caspases 4 and 5 function

Answer 16

Inflammation

Question 17

Caspase 14 function

Answer 17

Skin development

Question 18

Caspase cascade

Answer 18

. Sequential activation of 1 caspase after another in orderly fashion during apoptosis initiation
. Regulated by caspase inhibitors
. Initiated by apoptosome and death receptors activating initiator caspases
. Granzyme B released from Tc cells activates effector caspases

Question 19

Apoptosome activates which caspase?

Answer 19

9

Question 20

Death receptors activates which caspases?

Answer 20

8 and 10

Question 21

Granzyme B activates which caspases?

Answer 21

3 and 7

Question 22

Death effector domain

Answer 22

. Found in inactive photo-enzyme forms of certain initiator caspases and in proteins that regulate caspase activity (FADD, Fas-assoc. death domain containing protein)
. Recruits procaspases 8/10 into death-induced signaling complex DISC
. DISc requires 2nd DED in adaptor protein assoc. w/ TNF receptors
. Formation of complex allows proteolytic activation of the caspases and eventuates in apoptosis

Question 23

Targets of caspases

Answer 23

. Include nuclear and cytoplasmic proteins

. Nuclear lamins are structural fibrous proteins that are maint arteritis

Question 24

DNA during apoptosis

Answer 24

. DNA fragmentation factor 45/ inhibitor of caspase activated DNAase is cleaved
. Caspase activated DNAase enters nucleus and fragments DNA into ladder pattern

Question 25

T/F poly ADP ribose polymerase is proteolytically cleaved by caspases

Answer 25

T

Question 26

Bid

Answer 26

. Member of the Bcl-2 family | . Proteolytically cleaved by caspases

Question 27

Bcl-2 family

Answer 27

. Family of pro survival and pro apoptotic proteins . Pro survival: Bcl-2 and Bcl-xL . Pro death: Bak, Bid, Bax .

Question 28

What occurs after death receptor activates caspase-8?

Answer 28

. Catalyze cleavage of Bid into a truncated form (tBid) . Bak and Bax then translocate to outer mitochondrial membrane, permeabilize it, and facilitate release of pro-apoptotic proteins (cytochrome C and Smac that stop apoptosis inhibitors)

Question 29

What cancers have seen an overexpression of anto-apoptotic proteins in Bcl-2 family?

Answer 29

``` . Lymphoma . Breast cancer . Prostate cancer . Lung carcinoma . Melanoma ```

Question 30

Autoimmune conditions in relation to apoptosis

Answer 30

. T cells that recognizer self fail to undergo apoptosis

Question 31

Neurodegenerative illness in relation to apoptosis

Answer 31

. Altered apoptosis in schizophrenia . Localized apoptosis in Alzheimer’s can cause cognitive decline . HIV-associated dementia caused by caspase 3 activating in brain