Chapter 18: Apoptosis Flashcards
What is the normal relative concentration of the p53 protein in cells?
Low
This is an apoptosis gene regulatory protein that, when mutated, is located in 50% of all cancers
P53
This is a negative regulator of p53 and tends to inhibit transcriptional ability
MDM2
What are 3 things MDM2 does to p53?
- Inhibits transcriptional ability
- Favors p53 nuclear export
- Stimulates degredation
P53 mutation can do what 2 things to MDM2?
- Reduce MDM2 production
- Phosphorylate MDM2
What happens in a cell with a mutated p53 protein/gene?
Makes p53 incapable of responding to DNA damage properly by arresting in the cell in G1; can lead to cancer/tumor growth when it ignores apoptosis signals
When p53 behaves abnormally, where does it bind?
nowhere lol…she do be getting digested
P21 RNA translates to what?
Cyclin dependent kinase (cdk) inhibitor protein
What is the end protein that is inhibited with a mutated p53 gene/protein?
lol nothing
What are 3 reasons why cell prefer apoptosis over other types of cell death?
- Controlled and organized
- Timely
- Not as dmging at necrotic lysis
When is apoptosis induced in cells? (4)
- Mutations
- Dysfunction
- Immune system
- Development
Apoptosis in the immune system focuses on the destruction of what?
Non-functional immune cells/receptors to save enrgy
What are 5 basic steps of apoptosis?
- Cell shrinkage
- Cytoskeleton collapses
- Nuclear envelope dissassembly
- Nuclear DNA fragmentation
- Phagocytosis (via surface cell signals)
What 2 things is apoptosis dependent on?
- Energy capability
- mRNA machinery (to make protein)
A family of endoproteases that provide critical links in cell regulatory processes for apoptosis?
Caspases (cysteine-aspartic acid proteases)
This intercellilar character of apoptosis blocks cytochrome c release from mitochondria (blocks a route of apoptosis)
Bcl-2 protein
What does IAP stand for?
Inhibitor of apoptosis protein
This is a key molecule in the mitochondrial pathway of apoptosis; forms wheel of death (apoptosome)
APAF-1
This is released from mitochondria in response to death signals
Cytochrome c
What actions produce an active caspase ?
Dimerization, activation, and cleavage of inactive monomers
What induces the dimerization of caspases?
Adaptor proteins
The cleavage of an active caspase prodcues what? This product cleaves many substrates to induce apoptosis
Executioner caspases (3, 6, 7)
What are the two sources of death signals?
- Extrinsic
- Intrinsic
The activation of a cell’s surface death receptors is an example of what source of apoptosis signals?
Extrinsic
The activation of death receptors creates what protein complex?
DISC (death-inducing signal complex)
What does the DISC protein do?
Further cleavage and production of executioner caspases
This is a source of apoptosis signal that is received from within the cell itself
Intrinsic
What are 3 triggers of intrinsic apoptosis?
- Heat
- Excess radiation
- Viral infection
What are the 4 steps of basic intrinsic apoptosis?
- cytochrome c binds to APF-1
- Apoptosome assembly of APAF-1 aggregations (~7)
- Capsase 9 cleaving + dimerization
- Caspase executioner cascade occurs
What 3 things can override/out compete apoptosis signals?
- Inreased Bcl2
- BH3 inactivation
- Anti-IAP inactivation
