Question

1. Predict the effects of the following mutations on the ability of a cell to undergo apoptosis: (i) Mutation in Bad such that it cannot be phosphorylated by protein kinase B (PKB) (ii) Overexpression of Bcl-2 (iii) Mutation in Bax such that it cannot form homodimers.
2. One common characteristic of cancer cells is a loss of function in the apoptotic pathway. Which of the mutations listed above might you expect to find in some cancer cells?

Answer 1

1.Apoptosis is the programmed cell death of a cell.

(i)BAD is a pro-apoptotic protein of the Bcl-2 family. Phosphorylation of Bad could be one means of promoting cell survival. Thus if it cannot be phosphorylated by protein kinase B (PKB) it leads to Apoptosis turned on even in the presence of trophic factors. That is when it is unphosphorylated, it binds to Bcl-2/Bcl-xl and induces apoptosis.

(ii)BCL2 (member of the Bcl-2 family of regulator proteins) binds to and inactivates BAX and other pro-apoptotic proteins, thereby inhibiting apoptosis. Thus, when Overexpression of Bcl-2 happens cell survival occurs even in the absence of trophic factors. In other words Bcl-2 is anti-apoptotic so with a higher presence, there will be less of a chance for apoptosis to occur.

(iii)Bax is a member of the Bcl-2 family of proteins. Bax usually form homodimers which act as accelerators or inducers of cell death. Thus, when mutation in Bax such that it cannot form homodimers cell survival occurs even in the absence of trophic factors. In other words, it does not form an ion channel so the cytochrome c can bind to Apaf-1 - there is no initiation of apoptosis.

2. In some cancer cells, you might expect to find Overexpression of Bcl-2 and mutation in Bax such that it cannot form homodimers because both of these stops apoptosis, thus promoting chances of cancer formation which is the uncontrolled or unregulated growth of cells.