Term
What are the 4 roles of apoptosis? |
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Definition
1. sculpting tissue 2. Tissue homeostasis 3. Controlling cell numbers 4. Eliminating abnormal or harmful cells |
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Term
Describe the mechanism of apoptosis in mammals |
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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. |
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Term
How do caspases function? |
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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 |
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Term
how does the apoptosome form and what does it do? |
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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 |
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Term
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Definition
Genes that when activated promote excess cellular number or growth
Require one mutational event and are dominant gain of function |
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Term
What are tumor suppressor genes? |
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Definition
Genes that when inactivated can lead to excess cell number or growth
Require two mutational events (both alleles), recessive loss of function |
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Term
What are caretaker genes? |
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Definition
Genes responsible for maintaining the integrity of the genome. Their inactivation can lead to an increase in the mutation of other genes. |
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Term
What are the 6 characteristics of cancer? |
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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 |
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Term
What is the mechanism of Rous activation? |
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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. |
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Term
What are the mechanisms by which oncogenes become activated? |
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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 |
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Term
How do anti-oncogenes work? |
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Definition
Anti-oncogenes are genes whose protein expression serve to inhibit the function of oncogenes |
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Term
What is Knudson's "two-hit" hypothesis? |
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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). |
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Term
Mutations in what gene are likely involved in all forms of cancer? |
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Definition
Rb (a tumor suppression gene)
Mutations lead to rapid cell proliferation |
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