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18 Cards in this Set

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  • Back
What are caspases?

What are their 2 functional classes?
Proteases that affect cellular destruction

- Two functional classes: Initiators and Effectors (Executioners)
What is a procaspase?

How do they become active?
Inactive form of caspases located in the cytoplasm

- Become activated by proteolysis in response to apoptotic stimulus
What are the 2 pathway triggers for cell apoptosis?

What do they both use/involve?
1. Intrinsic Pathway - uses mitochondria and release of cytochrome C

2. Extrinsic Pathway - death receptor pathway (FAS-FASL)
What are the steps of the intrinsic pathway?
1. Cytochrome C released from mitchondira (KEY STEP)

2. Cytochrom C forms complex with Apaf-1, forms Apoptosome

3. Apoptosome, recruits procaspase - 9, forms wheel of DEATH

4. When activated caspase 9 cleaves and activates executioner caspases 3, 6, 7
What is the function of the Bcl family of proteins?

Function of Bcl-2 specifically?
Bcl protein family regulates cytochrome C release

Bcl-2 inhibits apoptosis by inhibiting release of cytochrome C from mitochondria

RECALL: Very important in Follicular Lymphoma!
What 2 proteins are pro-apoptotic and form physical pores in the mitochondrial membrane?

What protein inhibits them?
- Bak and Bax

- Inhibited by Bcl-2
What are the steps of the extrinsic pathway?
1. FAS-L binds to FAS receptor

2. Recruitment of FADD

3. FADD recruits initiator procaspases 8/10

4. Procaspases autoactivate and trigger effector caspases
What are the 3 main ways that cells can bypass apoptosis?
1. Over expressing anti-apoptotic proteins (Bcl-2)

2. Downregulating expression of pro-apoptotic proteins (Bax, Bak)

3. Losing p53, which indices pro-apoptotic proteins Bax, Puma, Nova
What are telomeres?

What enzyme created them?
Special, highly repeated sequences that protect the ends of linear chromosomes

- prevents degradation, translocation

Telomerase creates telomeres
What is the hayflick limit?
The number of divisions human cells can perform before senescing
When cells lose telomeres, what structure will form?

What does this induce in normal cells?

Cancer cells?
Break-fusion bridge cycle that generate amplifications, deletions, translocations

- In normal cells induce p53 but cancer cells typically don't have p53
What do cancer cells activate to stabilize damaged chromosomes?
Telomerase, although chromosomes are often highly aberrant
What 2 cancer "hallmarks" don't involve the cancer cells themselves?
1. Angiogenesis

2. Matastasis
What is angiogenesis?

What is the angiogenic switch?
Angiogenesis: formation of new blood vessels from existing ones

Angiogenic switch: point at which a tumor finds a way to recruit blood vessels from surrounding normal tissues, which can now supply tumor with nutrients and metastasis route
What are the characteristics of tumor vasculature?
Highly anomalous - chaotic blood flow, lakes, localized avascular regions, hypoxia
What is the main signal that promotes angiogenesis and is a current target of therapy?
Vascular Endothelial Growth Factor (VEGF)

Drug against: Avastin (bevacizumab)
Through what systems do cancer cells metastasize?
Blood AND lymphatic systems
What is the "soil and seed" concept of metastasis?
Seed refers to cancer cells, while the soul represents tissues with appropriate pool of GF's and ECM that support growth of cancer cells.

Some tumor cells live better in certain organs than others