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Cell Death
9/1/11 Second Lecture
13
Medical
Graduate
09/01/2011

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Cards

Term
What are the 4 roles of apoptosis?
Definition
1. sculpting tissue
2. Tissue homeostasis
3. Controlling cell numbers
4. Eliminating abnormal or harmful cells
Term
Describe the mechanism of apoptosis in mammals
Definition
Bcl-2 is an inhibitor of Apaf-1. Apaf-1 promotes Caspase, which causes apoptosis. When apoptosis is triggered, BH3-only inhibits Bcl-2, removing its inhibitory effect on Apaf-1.
Term
How do caspases function?
Definition
1. They are originally expressed as inactive pro-caspases
2. They cleave and destroy proteins essential for structure and survival
3. They also activate DNAse
Term
how does the apoptosome form and what does it do?
Definition
BH3 causes mitochondria to release Cytochrome C which binds to Apaf-1, which combines with other dimers to make the apoptosome.

The apoptosome is what cleaves pro-caspase to activate their apoptic functions
Term
What are oncogenes?
Definition
Genes that when activated promote excess cellular number or growth

Require one mutational event and are dominant gain of function
Term
What are tumor suppressor genes?
Definition
Genes that when inactivated can lead to excess cell number or growth

Require two mutational events (both alleles), recessive loss of function
Term
What are caretaker genes?
Definition
Genes responsible for maintaining the integrity of the genome. Their inactivation can lead to an increase in the mutation of other genes.
Term
What are the 6 characteristics of cancer?
Definition
1. Evading apoptosis
2. Self-sufficiency in growth signals
3. Insensitivity to anti-growth signals
4. Tissue invasion and metastasis
5. Sustained angiogenesis
6. Limitless replicative potential
Term
What is the mechanism of Rous activation?
Definition
The oncogene v-src (normally found in animal cells) is incorporated into the RSV (a virus) genome. When the virus invades a cell, it leads to overexpression of this gene leading to uncontrolled mitosis.
Term
What are the mechanisms by which oncogenes become activated?
Definition
1. Point mutation
2. Amplification of the gene
3. Translocation of the gene toward a strong promoter
4. Translocation to create fusion with a new protein
5. Proviral insertion
Term
How do anti-oncogenes work?
Definition
Anti-oncogenes are genes whose protein expression serve to inhibit the function of oncogenes
Term
What is Knudson's "two-hit" hypothesis?
Definition
Retinoblastoma is the outcome of mutated tumor suppression genes which are inherited from parents. In familial cases, one mutant allele is passed down, meaning only 1 more mutation is needed for cancer to proliferate. In sporadic cases, 2 mutations are needed (This is an example of a "loss of function" mutation, so a mutation on both alleles is necessary).
Term
Mutations in what gene are likely involved in all forms of cancer?
Definition
Rb (a tumor suppression gene)

Mutations lead to rapid cell proliferation
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