Question

1.) You are studying a particular type of cancer. You observe that the cells are expressing higher than normal levels of the activated version of the G protein Ras (ie, they contain more Ras-GTP than normal).

a.(2 pts) Further study shows that the one of the Ras genes has been mutated, would you classify this as the mutation of a tumor-suppressor gene or an oncogene?

b.(2 pts) Given your knowledge of the regulation of G proteins, suggest an explanation for how this mutant Ras protein results in more Ras-GTP than normal.

c.(2 pts) In a different cancer you also observe an increase in the activated form of Ras, however, in this case, the mutation has occurred in both copies of a gene encoding a protein that normally interacts with Ras. The mutant forms of the protein no longer interact with Ras and this leads to inappropriate growth. Since the mutation leads to cancer, would this loss of function be an example of an oncogene or a tumor-suppressor? Can you suggest a function for this protein?

Answer 1

1. a. Ras proteins are the GTPases and transmit signals within the cells. Mutation of these Ras genes produce permanently activated Ras proteins. Hence it acts as an oncogene when Ras gene is mutated.

b. As said above, the Ras gene mutation will permanently activate the Ras proteins and this lead the cell into an activation mode. Under activated state, the cell have active GTPases and they are constantly produced. Thus, mutant Ras protein results in more Ras-GTP than normal. This is a condition seen in cancer cells.

c. RAS proteins are involved in cellular signal transduction by a diverse set of protein–protein interactions, including effector molecules, such as RAF, phosphoinositide 3-kinase (PI3K) and Ral guanosine diphosphate dissociation stimulator. It is given that, the mutant forms of the protein no longer interact with Ras and this leads to inappropriate growth. Since the mutation leads to cancer, the loss of function is an example of oncogene. Hence, the protein may act in the suppression of the tumor production in the pathway and loss of this function lead to inappropriate growth.