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Apoptosis
Medical School Devo
25
Other
Graduate
09/04/2011

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Term
What are the two ways that cells die?
Definition
Necrosis and Apoptosis
Term
What are the key differences between necrosis and apoptosis?
Definition
Necrosis: break down of the membrane, causes inflammation

Apoptosis: programmed cell death. Cell will shrink due to membrane blebbing. Requires ATP
Term
What big role does apoptosis perform during development?
Definition
Apoptosis performs 2 key roles in development: Sculpting and Deleting vestigial organs

Sculpting: forming of fingers and toes

deleting: destroying the organs that existed solely for development (such as the allantois)
Term
What is the result of the failure of sculpting during development?
Definition
Syndactyly (fused digits) results from a failure of apoptosis
Term
What role does apoptosis perform in developed humans?
Definition
Maintaining homeostasis and eliminating abnormal, misplaced, nonfunctional, or harmful cells
Term
What are the four main signals that initiate apoptosis?
Definition
Loss of survival signals
Loss of contact signals
Irreperable internal damage
Instructive apoptosis
Term
What is instructive apoptosis?
Definition
Apoptosis after an immune response to lower levels of immune cells
Term
What are the two major pathways of apoptosis?
Definition
Membrane receptor pathway
and
Mitochondrial pathway
Term
What is the TNF superfamily?
Definition
This is the family of receptors on cell membranes that initiate apoptosis.

Stands for Tumor Necrosis Factor. Called Death Receptors
Term
What is the general pathway of apoptosis in membrane receptor pathway?
Definition
1) Signalling ligand binds to membrane receptors
2) Trimerization of receptor, Death domains in cell come together
3) Adapter protein (FADD) joins death domains
4) Adapter protein recruits procaspase through use of a death effector domain [DED, CARD]
5) Oligomerization and proteolytic activation of of initiator caspase
6) Further recruitment of effector caspases through cleavage by initiator caspases
Term
What caspases are initiator caspases?
Definition
2,8,9,10
Term
What caspases are effector caspases?
Definition
3,6,7
Term
Caspases only cleave when they recognize which compound?
Definition
Aspartic acid, highly specific
Term
Caspases have what on their active site?
Definition
Cystein residue
Term
Due to the proteolytic function of caspases, what checks are put in place to tightly regulate caspase function?
Definition
1) Synthesized as inactive precursors
2) inhibitors exist
Term
What do the inactive caspase precursors look like?
Definition
Have three segments: predomain, large domain, and small domain.

Dimerize to form active caspase
Term
What is the mechanism of mitochondrial initiated pathway for apoptosis?
Definition
1) Pro-apoptotic Bcl-2 family perforates the mitonchondrial membrane
2) Cytochrome C leaks out of mitochondrial membrane and binds to Apaf-1
3) Procaspase 9 binds to complex
4) Procaspase 3 binds to complex forming Apoptosome
5) Cleavage and subsequent activation
Term
What is the Apoptosome?
Definition
Protein complex formed by Procaspase 3, Procaspase 9, and Apaf-1 during mitochondrial initiated apoptosis
Term
What is Apaf-1?
Definition
Apoptotic protease activating factor
Term
What are the Proapoptotic factors of mitochondrial initiated apoptosis?
Definition
In cytosol:
Bax, Bak, Bad, Bim, Bid, Noxa, Puma

In mitochondria:
AIF
SMAC/Diablo
Cytochrome C
Term
What does AIF do?
Definition
Activates Caspase-3
Term
What does SMAC/Diablo do?
Definition
binds pro-caspase 3 inhibitors (IAPs)
Term
What are the anti-apoptotic factors in mitochondrial initiated apoptosis?
Definition
Bcl-2, Bcl-Xl, Mcl-1, Al/Bfl-1 and IAPs
Term
What do anti-apoptotic factors such as BCL-2 and Mcl-1 do?
Definition
Insert into the mitochondrial membrane and inhibit the release of Cytochrome C and other pro-apoptotic factors
Term
What do IAPs do?
Definition
IAPs = Inhibitors of Apoptosis

Bind to caspases and keep them inactive
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