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57 Cards in this Set

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T/F: Upstream activation of dimerized caspases (caspase-3) requires only cleavage.
False… only hetero-dimerization… since the dimers prior to activation are homodimers… no cleavage is needed.
What is the homologue of the worm death protein: Ced-3
Ced-3 = caspase family
What is the homologue of the worm death protein: Ced-4
Apaf-1 family
What is the homologue of the worm death protein: Ced-9
Bcl-2 family
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? Inflamation
necrosis
None
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? No inflammation
apoptosis
None
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? Programmed cell death (development)
apoptosis
None
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? Chaparone mediated
autophagy
None
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? Recycling of cellular substrates for energy
autophagy
None
What is the following cell death activity seen in apoptosis, necrosis, or autophagy? Fragments contained in cell
apoptosis
None
what is the following cell death activity seen in apoptosis, necrosis, or autophagy? Weakened membrane
necrosis
None
What connects the death receptor to the mitochondial pathway of apoptosis?
Bid
What activates Bid?
Caspase-8, cleaves it
What does Bid do in the mitochondrial pathway?
activates Bax, which is an apoptosis protein
None
Which of the following is not an apoptotic protein? Ced-3, Ced-4, or Ced-9?
Ced-9… Bcl-2, but not all are survival proteins
1.What are the Ced-9 proteins in humans?… 2. Which are pro-apototic and which are survival proteins?
1. Survival: Bcl-2 and Bcl-xl… 2. Apoptotic: BAX, BAC, Bid
None
Which of the death Bcl sub-families is a single domain? What it the domain, and what are the domains found in the other Bcl sub-families? (apoptotic only)
Bid=BH3… 2. BAX and BAK have BH1, BH2 and BH3
T/F: the Bcl sub-family activity is ubiquitous.
false, these proteins ar only active on the mitochondria, where they regulate cytochrome-C release
None
In mice, what does an Apaf-1 KO produce?
lack of digitation
In mice, what does a caspase-9 KO produce?
over-sized brain… no neuron depletion
What types of cellular organism exhibit necrosis?
metazoans (maybe more ancient organisms)
None
What types of cellular organism expresses apoptosis?
Metazoans
which types of cellular organism expresses autophagy?
unicellular eukaryotes, and metozoans
Where does macrophagy take place?
double membrane vessicle (plasma membrane)
What is the function of upstream caspases?
Upstream caspases cysteine proteases that cut proteins at specific residues, eg., caspase-8 and caspase-9 --> both cut caspase-3
None
1. On which amino acids do upstream caspases cut downstream caspases?... 2. What type of protease is an upstream caspase?
1. Upstream caspases cut proteins at aspartic acid residues... 2. cysteine protease
None
What is the active enzymatic site of cysteine protease? What is this site analogous to on the serine protease?
1. The sulfhydryl group… 2. It is analogous to the hydroxyl group on the serine protease.
T/F Upstream inactive caspases exist as uncut homodimers.
False, they exist as monomers, NOT dimers… cutting is not needed for activation
None
What is a procaspase?
an inactive caspase
How is an upstream procaspase activated?
forced (homo)-dimerization
None
T/F: downstream procaspases exist as uncut monomers
False, they exist as uncut dimers
None
How is a downstream procaspase activated?
cleavage
What can activate procaspase-3?
Caspase-8 or Caspase-9
None
What four things are necessary and sufficient to cause apoptosis? (hint)
1. ATP or dATP… 2. Apaf-1… 3. Caspase-9… 4. Cytochrome-C
Components of the mitochondrial death pathway
What is the role of Bcl-2 and Bcl-XL?
inhibits release of cytochrome-c from the mitochondria (survival.. Anti-apoptosis)
What is the role of Bac and Bac?
stimulates release of cytochrome-C from the mitochondria
T/F: Bax can be stimulated by internal stimulus.
True, but it can also be stimulated by external factors
What is the role of FADD in the DISC?
FADD serves as the adaptor protein in the death receptor, joining the receptor to the caspase-8, where forced dimerization now occurs
In the mitochondrial apoptosis pathway, what does the release of cytochrome-C cause?
Along with ATP (or dATP) it causes Apaf-1 to change shape and allows for the the recruiting and binding of Caspase-9 to create forced oligomerized homodimerization --> leading to caspase-9 activation --> which leads to caspase-3 cleavage --> which leads to apoptosis
None
What are the names of the Apaf-1 domains? Which ends are these domains at? (Hint: -COOH and -NH2)
WD-40 (COOH), Ced-9, Card (NH2)
What does the following Apaf-1 domain bind? Wd-40
cytochrome C
What does the following Apaf-1 domain bind? Ced-4
ATP (or dATP)
What does the following Apaf-1 domain bind? CARD
CARD on the caspase-9
T/F: procaspase-9 and procaspase-8 exists as an uncleaved homodimer
false, they exist as monomers and cleavage is not required
None
What is the role of XIAP?
XIAP inhibits caspase activation at Caspase-3, acvitated caspase-9, and the homodimerization of caspase-9/Apaf-1 complex
What activates the death receptor in apoptosis?
Fas lingand
What regulates XIAP?
SMAC,
Where is SMAC released from ?
mitochondria
Between XIAP and SMAC, which is pro-apoptotic?
SMAC=pro-apoptotic… XIAP=survival
What does FLIP do?
Inhibits the death receptor pathway
In APOPTOSIS here does cytochrome-c probably get released from on the mitochondria?… 2. which protein stimulate the release of cytochrome-C?... 3. Which proteins inhibit the release of cytochrome-c
1. A) mostly likely lipidic pores (maybe protein pores -OR- Perhaps VDAC-proteins transporters) 2. Bax/Bac... 3. Bcl-2/Bcl-XL
None
In NECROSIS where does cytochrome-c probably get released from on the mitochondria?… 2. What regulates the release of cytochrome-C?
1. Loss of outer mitochondrial membrane due to expansion of the inner mitochondrial membran… 2) no known regulation, however, because of opened ANT (ATP) transporters, ion flood the matrix causing loss of the ion-electric potential --> leading to inner mitochondrial expansion and expulsion of cytochrome-c into the cytosol.
None
Where does the FADD attach to on the Fas receptor?
on the death domain
What role does p53 play in apoptosis?
triggers cytochrome-c release (inhibits Bcl-2/Xl and stimulates Bax/Bac)
What is the role of Mdm2 and p19 (Arf)?
Mdm2 ihibits p53 and p19 inhibits Mdm2.
What clinical manifestation are seen in the absence of apoptosis?
Cancer and autoimune disorders
What might be done to avoid things like MI, neurodegenerative disease, and heart failure?
inhibit apoptosis