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Pharmacy BSI > BSI Lecture 24-26 Apoptotic Signaling > Flashcards

BSI Lecture 24-26 Apoptotic Signaling Flashcards

1
Q

Give 2 examples of intrinsic apoptotic signaling pathways.

A

1) mitochondrial-mediated apoptosis (mitochondrial dysfunction)
2) p53/Nuclear-mediated apoptosis

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2
Q

_____-_________ apoptosis utilizes Fas/FasL signaling.

A

Receptor mediated

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3
Q

Mitochondrial dysfunction can be caused by deficient ___ production.

A

ATP

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4
Q

Oxidative stress/ROS (reactive oxygen species) production is an example of ______ ________.

A

Oxidative dysfunction

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5
Q

When mitochondrial dysfunction is triggered, what does the mitocondrial release?

A

Cytochrome C

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6
Q

What does cytochrome C help initiate the formation of?

A

Apoptosome

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7
Q

What makes up a apoptosome?

A

Cytochrome C, Procaspase 9, dATP, and Apaf-1

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8
Q

Procaspase-9, is it active or inactive?

A

Inactive

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9
Q

What is the purpose of the apoptosome?

A

It’s going to lead to the activation of procaspase-9

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10
Q

How do you activate procaspase-9?

A

Formation of the apoptosome causes procaspase-9 to autocleave itself, resulting in more autocleaving of procaspase-9

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11
Q

Caspases are ________ which cleave other proteins.

A

proteases

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12
Q

What is considered the central executioner of apoptosis?

A

Caspase-3

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13
Q

What does caspase-9 do once it is activated?

A

It cleaves procaspase-3

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14
Q

What are the end results of Apoptosis?

A
  1. Destruction of cytoskeleton
  2. Destrution of nuclear envelope
  3. DNA fragmentation into mono- and oligonucleosomes
  4. Destruction/inactivation of pro-survival regulatory proteins.
  5. Membrane blebbing
  6. Formation of apoptotic bodies
  7. Apoptotic bodies engulfed by macraphages or neighboring cells.
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15
Q

How do macrophages or neighboring cells recognize apoptotic bodies?

A

The phoshatidylserine is flipped to the outter membrane.

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16
Q

The initiator caspase refers to caspase that initiates _________ ______.

A

caspase cascade

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17
Q

The _________ caspase will go and cleave a variety of things in the cell thats going to lead to the morphological characteristic of apoptosis.

A

executioner

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18
Q

What are the 3 categories of regulators of apoptosis?

A
  1. Bcl-2 Family
  2. Inhibitors of Apoptosis Proteins (IAPs)
  3. Repressors of IAPs
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19
Q

Anti-apoptotic and pro-apoptotic belongs to which regulatory group?

A

Bcl-2 family

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20
Q

What do anti-apoptotic proteins do?

A

prevent cytochrome c release

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21
Q

T or F? Bcl-2 and Bcl-XL are pro-apoptotic.

A

False, anti-apoptotic

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22
Q

What do pro-apoptotic proteins do?

A

favors cytochrome c release

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23
Q

T or F? Bax, tBid (truncated Bid), Bak, Bim. Bad, Bok are examples of pro-apoptotic group.

A

True

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24
Q

XIAP is an _______ of apoptosis proteins.

A

inhibitor (IAP)

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25
Q

What do IAPs do?

A

bind to cleaved caspases and inhibit activity

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26
Q

What does XIAP do?

A

Inhibits activity of caspase-9 and caspase-3

27
Q

Smac/Diablo and Omi/Htra2 are _______ of IAPs.

A

Repressors

28
Q

Where are Smac/Diablo and Omi/Htra2 released from?

A

Mitochondria upon stimulation

29
Q

What do Smac/Diablo and Omi/Htra2 do?

A

They bind IAPs and represses their inhibition on caspases allowing caspases to exhibit their activitiy to execute apoptosis.

30
Q

T or F? The ratio between Bcl-2 and Bax will determine whether or not cytochrome c will be released.

A

true

31
Q

T or F? Bcl-2 forms a pore that cytochrome c can pass through to go into the cytosol.

A

false, Bax not Blc-2

32
Q

What protein(s) inhibits Bax from creating a pore?

A

Blc-2 or any anti-apoptotic proteinT or F?

33
Q

T or F? ICAD binds to CAD and inhibits its activity during apoptosis.

A

false, while not undergoing apoptosis

34
Q

How does XIAP inhibit apoptosis?

A

Binds to caspase-9 and caspase-3 to inhibit their activity

35
Q

How does BCL2 inhibit apoptosis?

A

Inhibits Bax oligomerization and cytochrome c release

36
Q

T or F? Smac/Diabo is an anti-poptotic protein

A

false, repressors of IAPs

37
Q

______ binds to CAD when cells are not undergoing apoptosis

A

ICAD

38
Q

Cells undergoing apoptosis, caspases-3 cleaves and inactivates ______.

A

ICAD

39
Q

When ICAD is cleaved, _____ will then be active.

A

CAD

40
Q

______ will go and fragment DNA into mono- and oligonucleosomes.

A

CAD

41
Q

___________ inactivates proteins involved in DNA repair

A

Caspase-3

42
Q

__________ will cleave cytoskeleton (actin) and cause shrinkage of the cell and membrane blebbing.

A

Caspase-3

43
Q

T or F? Caspase-3 inactivates anti-apoptotic BCL-2 family proteins by cleavage.

A

True

44
Q

____ ______ leads to an increase or accumulation of p53.

A

DNA damage

45
Q

T or F? p53 speeds up the cell cycle.

A

False, halts

46
Q

______ plays a role in stimulating DNA repair.

A

p53

47
Q

p53 induces translocation of Bax to mitochondria resulting in ____________ _______ _________

A

cytochrome c release

48
Q

T or F? p53 also alters transcription of pro-apoptotic and anti-apoptotic genes.

A

True

49
Q

p53 _______ pro-apoptotic transcription.

A

increases (Bax, Fas, Apaf-1, etc)

50
Q

p53 _______ anti-apoptotic transcription.

A

decrease (Bcl-2, Bcl-XL, survivin, etc)

51
Q

How does DNA damage lead to the accumulation of p53

A

ATM and ATR kinases will phospphorylate p53, which prevents MDM2 (ubiquitin ligase). (p53 acts a transcription factor, increasing the transcription of p21 (cyclin CDK inhibitor). P21 then binds to G1/S-CdK and S-CDK inhibiting their activity)

52
Q

Cytotoxic T cells expresses _____ in its surface.

A

FasL

53
Q

Target cell expresses ____ (receptor) on its surface

A

Fas

54
Q

T or F? A receptor-mediated apoptosis involves using a ligand.

A

True

55
Q

in the t-cell example, can they both express FasL and Fas?

A

yes

56
Q

T or F? Fas on cytotoxic T cells binds FasL receptor on target cell and induces apoptosis.

A

False, FasL on cytoxic t cells and Fas on receptor

57
Q

When FasL binds to the receptor, it trimerizes, then ______ is recruited to the receptor.

A

FADD

58
Q

When recruited to the receptor, FADD recruits _________

A

Procaspase-8

59
Q

What does DISC stand for?

A

Death Inducing Signaling Complex

60
Q

What does the DISC consist of?

A

Fas receptor, FADD, Caspase 8

61
Q

_____________ are brought in close proximity by DISC and then they auto cleave each other.

A

Procaspase-8

62
Q

Caspase 8 cleaves and activates ____________ and _____

A

Caspase-3/Bid

63
Q

What does c-flip do?

A

Inhibits activation of caspase-8

64
Q

Receptor-mediated apoptosis; Why do some cells require caspase-8 to cleave BID?

A

Cells that has high expression of XIAP needs smac/diablo omni/htra2 to inhibit those XIAP for apoptosis to occur

Pharmacy BSI (58 decks)

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