Question

Question: A cell can initiate both pro- and anti- apoptotic signals in response to a stimuli. Given each scenario, choose the most likely protein to counteract the “cell death signal” and save the cell. To save the cell you must choose the best strategy (Best = most direct, so if we disrupt A we should fix A or possibly B instead of trying to fix D.) Pick a strategy for the scenario:

1.Activated Caspase 9

2.Activated Bax and Bak

3.Release of cytochrome C in the cytosol

4.Caspase mediated DNA double stranded breaks

5.Apoptosome formation

6.Death ligand expression in neighboring cells.

options for each senario:

a.Bcl2 - stabilizes mitochondrial outer membran. b. IAPs - target caspases for degradation c.There is no hope of cell survival d.Stabilize the cell membrane e.Block death receptor trimerization.

Answer 1

1.Activated Caspase 9: IAPs - target caspases for degradation.

Once activated, caspase-9 would cleave and activate caspase-3 which in turn cleave vital proteins, DNA, and induce membrane blebbing. IAPs are inhibitors of apoptosis; they bind to caspases and target them for degradation.

So, if the caspae-9 is activated, we can counter it by introducing IAPs to save the cell.

2.Activated Bax and Bak: Bcl2 - stabilizes mitochondrial outer membrane.

Bax and Bak form homo- or hetreodimers and bind to the mitochondrial membrane to create pores through which cytochrome-c will be released. This cytochrome-c would then bind to pro-caspase-9 and Apaf-1 to form apoptosome complex leading to activation of caspase-9.

Bcl-2 is an anti-apoptotic protein that prevents Bax and Bak from forming dimers (pores).

So, when Bax and Bak are activated, we can counter it by introducing Bcl-2 to save the cell.

3.Release of cytochrome C in the cytosol: IAPs - target caspases for degradation.

Cytochrome C activates caspase-9. IAPs inhibit caspas-9 by targeting it to degradation.

So, if the cytochrome c is released in the cytosol, we can counter it by introducing IAPs to save the cell.

4.Caspase mediated DNA double stranded breaks: There is no hope of cell survival.

If caspases mediate DNA cleavage, then there is no hope for cell survival.

5.Apoptosome formation: IAPs - target caspases for degradation.

Apoptosome formation activates caspase-9. IAPs target caspase-9 for degradation.

So, if the apoptosome complex is formed, we can counter it it by introducing IAPs to save the cell.

6.Death ligand expression in neighboring cells: Block death receptor trimerization.

Death ligands binds to death receptors to induce extrinsic apoptosis.

So, if death ligand is expressed in neighboring cells, we can counter it by blocking death receptor trimerization to save cells.