Lecture 30 Flashcards
Describe the function of BH123. (include a description of the number of domains, where it is found, active and inactive states, and what exactly active BH123 does)
BH123 is a pro-apoptotic protein that triggers the intrinsic apoptosis pathway if it is activated
it has 4 domains in the outer mitochondrial membrane that are separated when inactive and aggregate when activated
When activated, BH123 induces the release of cytochrome c and then binds to Apaf1 to form an apoptosome
Describe the function of Bcl2 (include it’s location, types, and how exactly it carries out it’s function)
it regulates the intrinsic apoptosis pathway by controlling the release of cytochrome c into the cytosol
it is found on the cytosolic surface of the outer mitochondrial membrane
Anti-apoptotic Bcl2: blocks the release of cytochrome c to promote cell survival
Pro-apoptotic Bcl2: promotes the release of cytochrome c
Describe the function of BH3-only (what is necessary for BH3 activity, where is it found/action take place)
BH3 doesn’t do anything until it is activated
after activation, it moves from the cytosol, to the mitochondria where it helps to activate the intrinsic apoptosis pathway
BH3-only inhibits “anti-apoptotic Bcl2 proteins” and basically inhibits the inhibiting Bcl2 protein
This allows the activation of the intrinsic apoptosis pathway and therefor makes BH3-only a “pro-apoptotic”protein
What are IAP’s and what is their function? (be sure to state the 2 methods it has for completing it’s function and what “issue” this addresses)
Inhibitors or Apoptosis = IAP
they bind to caspases to block them, or ubiquitinate them to destroy them (either way they prevent the function of caspases)
(this solves the issue of Caspases being able to auto-activate themselves)
What are anti-IAP’s and what is their function? (include their origin)
They are proteins from the mitochondria that block the function of IAPs
This allows the apoptosis pathway to occur
Describe what is the role of of Bcl2 protein in apoptosis?
it regulates the intrinsic apoptosis pathway by controlling the release of cytochrome c into the cytosol
Anti-apoptotic Bcl2: blocks the release of cytochrome c to promote cell survival
Pro-apoptotic Bcl2: promotes the release of cytochrome c
Describe what is the role of of Bcl2 protein in apoptosis? (be specific)
it regulates the intrinsic apoptosis pathway by controlling the release of cytochrome c into the cytosol
Anti-apoptotic Bcl2: blocks the release of cytochrome c to promote cell survival by binding to and inhibiting the aggregation of pro-apoptotic proteins
Pro-apoptotic Bcl2: promotes the release of cytochrome c through the outer mitochondrial membrane
describe the molecular structure of the 2 types of Bcl2 proteins
Anti-apoptotic Bcl2: has 4 distinctive domains called Bcl homology domains (BH domains)
Pro-apoptotic Bcl2: includes BH123 protein and BH-3 only protein
BH123 protien has 3 domains
BH3-only protein has only 1 domain
List the 4 functions of executioner caspases
cleaves downstream proteins
cleaves inactive endonuclease
Targets cytoskeleton
Attacks cell adhesion proteins
List the 4 functions of executioner caspases
cleaves downstream proteins
cleaves inactive endonuclease
Targets cytoskeleton
Attacks cell adhesion proteins
True or False: The caspase cascade is irreversible. explain
True
In general, describe caspases.
Cystein aspartyle specific protease
targets proteins and cleaves them along their aspartic AA residues
They have Cysteine in their active site
describe the maturation process of a caspase
first synthesized as an inactive “procaspase”
an active caspase then cleaves the “prodomains” off of the procaspase
the large and small subunits (what is left after prodomain cleavage) then come together to form a heterodimer that is an active caspase
True or false: Large quantities of Caspases are synthesized prior to apoptosis activation. explain
False
caspases are always present in all cells, they simple wait to be activated by an internal or external stimuli
(initiator caspases can auto-activate as well and thats no bueno)
In terms of apoptosis pathways, the intrinsic pathway is mitochondria _____ and the extrinsic pathway is mitochondria _____.
dependent
independent
Explain the molecular structure and presentation of death receptors within a cell membrane
They are transmembrane proteins with 3 domains
An extracellular binding domain
A single transmembrane domain
An intracellular death domain
they exist in homotrimers (3 proteins of the same type that remain associated with one another)
Explain the Extrinsic apoptotic pathway (starting with Fas, ending with executioner caspase)
Fas ligand binds to death receptor on the cell surface (both are homotrimers)
death receptor’s intracellular”death domain” recruits FADD (Fas associated death domain) and procaspase-8
a trimer of FADD and procaspase-8 come together to form DISC (death inducing signal complex)
The formation of DISC activates (cleavage into mature caspase) procaspase-8
active caspase activates downstream executioner caspase (caspase-3)
Describe and state the function of Decoy receptors and FLIP.
Decoy receptors: basically mimic death receptors on the surface of a cell, however they bind to the Fas ligand and then DO NOT activate apoptosis
FLIP: is a protein that resembles an initiator procaspase and competitively inhibits procaspase-8 and procaspase-10.
(both resemble apoptotic pathway molecules, but prevent apoptosis “act as sponges”)
Explain the intrinsic apoptotic pathway
cytochrome c is released from the mitochondria, into the cytosol where it binds to Apaf1
several Apaf1 (apoptotic protease activating factor-1) bound to cytochrome c, come together to form an apoptosome
The apoptosome activates caspase-9 (initiator caspase)
Caspase-9 activates caspase-3 which is an executioner caspase that begins it’s apoptotic activities
Name an executioner caspase that is common to both the intrinsic and extrinsinc apoptotic pathways.
caspase-3
Chromosome translocation can occur and cause excessive ____ to be made, which causes B cell lymphoma
Bcl2
Give 2 examples of condition that occur as a result of excessive apoptosis
heart attacks and strokes
If p53 is mutated to the point that it can no longer carry out it’s normal functions, what happens to the cell?
apoptosis is no longer promoted by p53 so cancer can develop
