A current focus of molecular medicine is to trigger or prevent apoptosis in spec
ID: 67773 • Letter: A
Question
A current focus of molecular medicine is to trigger or prevent apoptosis in specific cells. Several components of the apoptotic pathway are being targeted using this approach. For each of the following, state specifically how the treatment would be expected to stimulate or inhibit apoptosis.
Part A: Cells are treated with a small molecule called pifithrin-, which was originally isolated for its ability to reversibly block p53-dependent transcriptional activation. Select the 3 correct Statement.
1) In such cells, division would be less likely to occur, and they would be more likely to enter apoptosis. 2) p21 would be expressed, leading to cell cycle arrest
3)Puma would be expressed, leading to more efficient inhibition of mitosis.
4)In such cells, apoptosis would be less likely to occur, and they would be more likely to divide.
5) p21 would not be expressed, leading to loss of cell cycle arrest.
6) Puma would not be expressed, leading to more efficient inhibition of mitosis.
Part B: Exposing cells to recombinant TRAIL protein, a ligand for the tumor necrosis factor family of receptors.
1)TRAIL would activate pathways similar to Apaf-1, a known stimulator of apoptosis.
2) TRAIL would activate pathways similar to Bcl-2, a known survival factor.
3) TRAIL would activate pathways similar to TNF-, a known stimulator of apoptosis.
4) TRAIL would activate pathways similar to PIP3, a known survival factor.
Part C: Treatment of cells with organic compounds that enter the cell and bind with high affinity to the active site of caspase-3.
1) Caspase-3 is a key inhibitor of the apoptosis pathway, so inhibiting it would promote cell death.
2) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress cell death.
3) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would promote the cell cycle arrest.
4) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress the cell cycle arrest.
1) In such cells, division would be less likely to occur, and they would be more likely to enter apoptosis. 2) p21 would be expressed, leading to cell cycle arrest
3)Puma would be expressed, leading to more efficient inhibition of mitosis.
4)In such cells, apoptosis would be less likely to occur, and they would be more likely to divide.
5) p21 would not be expressed, leading to loss of cell cycle arrest.
6) Puma would not be expressed, leading to more efficient inhibition of mitosis.
Part B: Exposing cells to recombinant TRAIL protein, a ligand for the tumor necrosis factor family of receptors.
1)TRAIL would activate pathways similar to Apaf-1, a known stimulator of apoptosis.
2) TRAIL would activate pathways similar to Bcl-2, a known survival factor.
3) TRAIL would activate pathways similar to TNF-, a known stimulator of apoptosis.
4) TRAIL would activate pathways similar to PIP3, a known survival factor.
Part C: Treatment of cells with organic compounds that enter the cell and bind with high affinity to the active site of caspase-3.
1) Caspase-3 is a key inhibitor of the apoptosis pathway, so inhibiting it would promote cell death.
2) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress cell death.
3) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would promote the cell cycle arrest.
4) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress the cell cycle arrest.
Explanation / Answer
Part A:
4)In such cells, apoptosis would be less likely to occur, and they would be more likely to divide.
5) p21 would not be expressed, leading to loss of cell cycle arrest.
6) Puma would not be expressed, leading to more efficient inhibition of mitosis
p53 is a tumor suppressor gene. In the absence of the function of P53, p21 protein is not available to act as stop signal for cell division. Therefore, cell cycle is not arrested. Loss of p53 also causes the cells not to commit apoptosis.
Part - B:
3) TRAIL would activate pathways similar to TNF-, a known stimulator of apoptosis.
When the ligand binds to the TNF family receptors, the pathway initiates cytochrome c in the cytosol to bind the adaptor TNF-, leads to formation of apoptosome that activates apoptosis initiating preotase caspase-9, and promotes apoptosis by binding the aposotis inhibitor (IAP).
Part-C:
2) Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress cell death.
Caspase 3 is one of the factors that activate apoptosis. When activated by intrinsic activators like cytochromoe c, caspase 3 works along with caspase 9, Apaf-1, XIAP, towards the process of apoptosis of the cell. Inhibiting this protein results in suppression of cell death.
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