3.3 Apoptosis Flashcards
What are 7 characteristics of apoptosis?
- shrinkage in volume of cell and nucleus. 2. Loss of adgesion to neighboring cells. 3. formation of blebs on surface. 4. DNA fragmentation. 5. Cyctoskeleton collapses. 6. Nuclear envelope disassembles. 7. Rapid engulfment of dying dying cell by phagocytosis.
What is a marker of apoptosis?
Cytochrome C released from mitochondria
What mediates Apoptosis?
Caspases
What does Caspase do?
Targets proteins and cleaves them in their seq where an aspartic AA residue occurs/
What is a key event in apoptosis?
Activation of caspases
What are procaspases?
Caspases synthesized first as an inactive precursor
How do procaspases get activated?
By protease cleavage.
True or False? Caspses activate procaspases
True
What are the two major classes of caspases?
Initiator and executioner caspases
What does initiator caspase do?
Initiates apoptosis
What do Executioner caspases do?
destroy actual targets, executes apoptosis.
True or False? Caspase cascade is reversible
False. IRREVERSIBLE
What are the 2 apoptosis pathways?
Internal and external pathway
When is internal pathway used?
Abnormalities in DNA
When is external pathway used?
Removal of survival factors and proteins of tumor necrosis factor family
From the 2 apoptosis pathways, which is mitochondrial dependent and independent?
Intrinsic is mitochondrial dependent. Extrinsic is mitochondrial independent.
How does the extrinsic pathway activate?
Extracellular signals bind to cell surface death receptors and trigger extrinsic pathway
True or False death receptors are homotrimers?
True
What does homotrimer mean?
3 proteins of same type
What is the first step in the extrinsic pathway of apoptosis?
Fas binds to Fas death receptor
What is the 2nd step in the extrinsic pathway of apoptosis?
FADD adaptor and procaspase-8 with death effector domain recruited
What is the 3rd step in the extrinsic pathway of apoptosis?
Form trimers, bring death domains together forming DISC.
What is the 4th step in the extrinsic pathway of apoptosis?
caspase 8 or 10 activated. Which activated executioner caspases. Caspase 3. Apoptosis happens.
how is the intrinsic pathway activated?
response to injury, DNA damage, etc.
What is the first major key event in the intrinsic pathway?
translocation of cytochrome c from mitochondria to cytosol.
What is the 2nd step of the intrinsic pathway?
Cytochrome c binds to Apaf1.
What is the 3rd step of the intrinsic pathway?
Apaf1 forms apoptosome which activates caspase-9
What is the 4th step of the intrinsic pathway?
Caspase-9 activates downstream executioner caspases. ex caspase 3.
What family of proteins regulates the intrinsic pathway?
BCL2 family
How does the BCL2 family control the intrinsic pathway?
BCL2 controls release of cytochrome c into cytosol
What are the two types of BCL2 proteins?
anti apoptotic and pro apoptotic
What do anti apoptotic proteins do?
Blocks release of cytochrome C
What does pro apoptotic proteins do?
promotes release of cytochrome c
What are 2 ex of anti apoptotic proteins?
BCL@ and BCL-XL
What are 2 ex of pro apoptotic BH123 proteins?
BAX and Bak
what are 2 ex of pro apoptotic BH3-only proteins?
Bad, Bim.
What are the steps when BH123 is activated?
BH123 proteins activated, form aggregation in mitochondrial outer membrane and release cytochrome C. Apoptosome formed by binding to Apaf1.
How do anti apoptotic proteins stop apoptosis?
By binding to pro aopototic proteins like BH123 and preventing aggregation into active form
Where are anti apoptotic proteins located in the cell?
Cytosolic surface of outer mitochondrial membrane
Where is an activated Pro apoptotic BH3 only protein located? Where does it translocate after apoptotic signal?
Cytosolic. To mitochondria
How does BH3 only pro apoptotic proteins induce apoptosis?
Stop anti apoptotic BCL2 protein from inhibiting aggregation to release cytochrome C.
What two things do IAPs inhibit?
Apoptosis and caspases
How do IAPs inhibit Apoptosis and caspases?
IAPs add ubiquitin to caspases or bind to caspases themselves to stop apoptosis.
Why are IAPs a good thing?
Solves the auto activating caspases problem
What releases anti IAPS?
apoptotic stimuli or signals
What do anti IAPs do?
block activity of IAPs
What happens when IAPs are blocked by anti IAPs?
Executioner caspases can be activated
Where did BCL2 get its name?
Where it was found, B cell lymphoma
What can cause excessive BCL2 to be made?
chromosome translocation
What happens when theres excess of BCL2?
BCL2 is inhibitor of apoptosis therefore theres insufficient apoptosis. Can cause cancer.
Describe some of the cellular characteristics of apoptosis*
Formation of blebs, DNA fragmentation, cytoskeleton collapses.
Describe what is the role of BCL2 protein in apoptosis*
regulates the intrinsic pathway of apoptosis by controlling release of cytochrome c into cytosol.
Describe the two major forms of caspases*
Initiator: Initiates apoptosis and executioner caspases: destroy actual targets, executes apoptosis.
