Exam 3 - Apoptosis Flashcards
1
Q
What are some cellular characteristics of apoptosis ?
A
- Def
- is a routine controlled cell death that minimizes spread of damage and/or inflammation
- contents dont leak out
- Shrinkage in volume of the cell and its nucleus
- loss of adhesion to neighboring cells
- formation of blebs on surface
- DNA fragmentation
- Cytoskeleton collapses
- nuclear envelope disassembles
- rapid engulfment of dying cell by phagocytosis (macrophages)
2
Q
What role does bcl2 Protein in apoptosis?
A
3
Q
What are the two major forms of caspases ?
A
- Initiator Caspase:
- initiates apoptosis by activating executioner caspases
- Executioner Caspases
- destroys actual targets - executes apoptosis
- cleaves downstream proteins
- cleaves inactive endonucleases
- targest sytoskeleton
- attacks cell ashesion protein and cell roles up in ball
4
Q
what are caspases?
A
- Apoptosis is an intracellular proteolytic cascade mediated by this protease
- activation of caspases is a key event in apoptosis
- Caspase = Cysteine ASPartyl specfic proteASE
- Cysteine in active site
- targets proteins and cleaves them in their sequence where an aspartic amino acid residue occurs
5
Q
What is the caspase cascade?
A
- Caspase Cascade is irreversible
- machinary for apoptosis always in place
- Initiator caspase autoactivates itself
- Excecutioner caspases cleaves cellular targets
6
Q
What are the two apoptosis pathways?
A
depend on factors that induce apoptosis
- internal stimuli
- abnormalities in DNA
- External Stimuli
- removal of survival factors and proteins of tumor necrosis factor family
- Intrensic pathway is mitochondral dependent
- Extrinsic pathway is mitochondrial independent
7
Q
What is the extrinsic pathway?
A
- Extracellular signals binds to cell surface death receptors and trigger extrensic pathway
- Death receptors are transmembrane proteins with 3 domains
- extracellular
- single transmembrane domain
- intracellular deathdomain
- Receptors are homotrimers three proteins of same type (members of TNF family of proteins tumor necrosis factor)
8
Q
What are ways to inhibt the extrinsic pathway?
A
9
Q
What is the Intrinsic Pathway?
A
10
Q
What regulates to intrinsic pathway?
A
- Bcl2 protein family
- anti-apoptotic
- (pro survival) blocks release of cytochrome C :
- 4 distinct domains called bcl homology “BH” domains
- mainly located on cytisolic surface of outer mitochondrial embrane
- Ex : bcl2 and Bcl-XL
- binds to pro-apoptic proteins and and prevent aggregation into active form
- Pro-Apoptotic
- promotes release of cytochrome C
-
Ex: Bh123
- bax, bak
- Ex: Bh3 (inhibits anti-apoptotic Bcl2)
- cytosolic
- translocates to mitchondria after apoptotic signals activates it
- bas, bim, bid, puma, noxa
11
Q
What is the difference between IAP and Anti-IAPs?
A
- IAP: Inhibitors of Apoptosis
- Bind and inhibit caspases
- some added ubiquitin to caspases
- Blocks apoptotsis by binding to caspases
- prevents caspases autoactivating
- Anti-IAPs
- Apoptotic stimuli or apoptosis signals
- relase of anti-laps from mitochodria to block activity of IAPs
- Allowing executioner caspases can therefor be activated with IAPS blocked
12
Q
What cause B cell lymphoma?
A
- Due chromosome translocation that causes excessive Bcl2 to be made: Bcl2 is inhibitor of apoptosis
- promotes development of cancer by inhibiting apoptosis
- DNA damaged cells will not be programmed for cell death and go on to cause cancer
13
Q
What does a p53 mutation cause
A
- Mutated p53 can no loner causes cell arrest
- insufficient and no longer promotes apoptosis
- cells with damage stick around and cancer can be generated
Random fact not related to question
In general, excessive apoptosis can be a probelm it occurs in heart attacks and strokes
