BSI Lecture 24-26 Apoptotic Signaling Flashcards
Give 2 examples of intrinsic apoptotic signaling pathways.
1) mitochondrial-mediated apoptosis (mitochondrial dysfunction)
2) p53/Nuclear-mediated apoptosis
_____-_________ apoptosis utilizes Fas/FasL signaling.
Receptor mediated
Mitochondrial dysfunction can be caused by deficient ___ production.
ATP
Oxidative stress/ROS (reactive oxygen species) production is an example of ______ ________.
Oxidative dysfunction
When mitochondrial dysfunction is triggered, what does the mitocondrial release?
Cytochrome C
What does cytochrome C help initiate the formation of?
Apoptosome
What makes up a apoptosome?
Cytochrome C, Procaspase 9, dATP, and Apaf-1
Procaspase-9, is it active or inactive?
Inactive
What is the purpose of the apoptosome?
It’s going to lead to the activation of procaspase-9
How do you activate procaspase-9?
Formation of the apoptosome causes procaspase-9 to autocleave itself, resulting in more autocleaving of procaspase-9
Caspases are ________ which cleave other proteins.
proteases
What is considered the central executioner of apoptosis?
Caspase-3
What does caspase-9 do once it is activated?
It cleaves procaspase-3
What are the end results of Apoptosis?
- Destruction of cytoskeleton
- Destrution of nuclear envelope
- DNA fragmentation into mono- and oligonucleosomes
- Destruction/inactivation of pro-survival regulatory proteins.
- Membrane blebbing
- Formation of apoptotic bodies
- Apoptotic bodies engulfed by macraphages or neighboring cells.
How do macrophages or neighboring cells recognize apoptotic bodies?
The phoshatidylserine is flipped to the outter membrane.
The initiator caspase refers to caspase that initiates _________ ______.
caspase cascade
The _________ caspase will go and cleave a variety of things in the cell thats going to lead to the morphological characteristic of apoptosis.
executioner
What are the 3 categories of regulators of apoptosis?
- Bcl-2 Family
- Inhibitors of Apoptosis Proteins (IAPs)
- Repressors of IAPs
Anti-apoptotic and pro-apoptotic belongs to which regulatory group?
Bcl-2 family
What do anti-apoptotic proteins do?
prevent cytochrome c release
T or F? Bcl-2 and Bcl-XL are pro-apoptotic.
False, anti-apoptotic
What do pro-apoptotic proteins do?
favors cytochrome c release
T or F? Bax, tBid (truncated Bid), Bak, Bim. Bad, Bok are examples of pro-apoptotic group.
True
XIAP is an _______ of apoptosis proteins.
inhibitor (IAP)
What do IAPs do?
bind to cleaved caspases and inhibit activity
What does XIAP do?
Inhibits activity of caspase-9 and caspase-3
Smac/Diablo and Omi/Htra2 are _______ of IAPs.
Repressors
Where are Smac/Diablo and Omi/Htra2 released from?
Mitochondria upon stimulation
What do Smac/Diablo and Omi/Htra2 do?
They bind IAPs and represses their inhibition on caspases allowing caspases to exhibit their activitiy to execute apoptosis.
T or F? The ratio between Bcl-2 and Bax will determine whether or not cytochrome c will be released.
true
T or F? Bcl-2 forms a pore that cytochrome c can pass through to go into the cytosol.
false, Bax not Blc-2
What protein(s) inhibits Bax from creating a pore?
Blc-2 or any anti-apoptotic proteinT or F?
T or F? ICAD binds to CAD and inhibits its activity during apoptosis.
false, while not undergoing apoptosis
How does XIAP inhibit apoptosis?
Binds to caspase-9 and caspase-3 to inhibit their activity
How does BCL2 inhibit apoptosis?
Inhibits Bax oligomerization and cytochrome c release
T or F? Smac/Diabo is an anti-poptotic protein
false, repressors of IAPs
______ binds to CAD when cells are not undergoing apoptosis
ICAD
Cells undergoing apoptosis, caspases-3 cleaves and inactivates ______.
ICAD
When ICAD is cleaved, _____ will then be active.
CAD
______ will go and fragment DNA into mono- and oligonucleosomes.
CAD
___________ inactivates proteins involved in DNA repair
Caspase-3
__________ will cleave cytoskeleton (actin) and cause shrinkage of the cell and membrane blebbing.
Caspase-3
T or F? Caspase-3 inactivates anti-apoptotic BCL-2 family proteins by cleavage.
True
____ ______ leads to an increase or accumulation of p53.
DNA damage
T or F? p53 speeds up the cell cycle.
False, halts
______ plays a role in stimulating DNA repair.
p53
p53 induces translocation of Bax to mitochondria resulting in ____________ _______ _________
cytochrome c release
T or F? p53 also alters transcription of pro-apoptotic and anti-apoptotic genes.
True
p53 _______ pro-apoptotic transcription.
increases (Bax, Fas, Apaf-1, etc)
p53 _______ anti-apoptotic transcription.
decrease (Bcl-2, Bcl-XL, survivin, etc)
How does DNA damage lead to the accumulation of p53
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)
Cytotoxic T cells expresses _____ in its surface.
FasL
Target cell expresses ____ (receptor) on its surface
Fas
T or F? A receptor-mediated apoptosis involves using a ligand.
True
in the t-cell example, can they both express FasL and Fas?
yes
T or F? Fas on cytotoxic T cells binds FasL receptor on target cell and induces apoptosis.
False, FasL on cytoxic t cells and Fas on receptor
When FasL binds to the receptor, it trimerizes, then ______ is recruited to the receptor.
FADD
When recruited to the receptor, FADD recruits _________
Procaspase-8
What does DISC stand for?
Death Inducing Signaling Complex
What does the DISC consist of?
Fas receptor, FADD, Caspase 8
_____________ are brought in close proximity by DISC and then they auto cleave each other.
Procaspase-8
Caspase 8 cleaves and activates ____________ and _____
Caspase-3/Bid
What does c-flip do?
Inhibits activation of caspase-8
Receptor-mediated apoptosis; Why do some cells require caspase-8 to cleave BID?
Cells that has high expression of XIAP needs smac/diablo omni/htra2 to inhibit those XIAP for apoptosis to occur
