Question

Which of the following alterations would likely contribute to the formation of a cancerous somatic cell? Fill in all correct answers if there are more than one.

A.Mutations in cyclin-dependent kinase genes that made the catalytic activity of the kinases cyclin-independent.

B.A mutation that inactivated expression of the gene that encoded the protein that de-phosphorylated the RB protein

C.A mutation in the p53 transcription factor binding site near the Bax gene promoter that eliminated p53 binding.

D.A mutation in the Mdm2 gene that eliminated the ability of the MDM2 protein to bind to p53.

E.A mutation in the Retinoblastoma (Rb) gene that eliminated the phosphorylation site on the RB protein.

F.A mutation in the Ras gene that eliminated the GTPase activity of the RAS protein.

G.A mutation in the Ras gene that generated a RAS protein that would not release bound GDP.

H.Mutations in the p53 gene that eliminated the sites of phosphorylation and acetylation on the p53 protein.

Answer 1

The correct options are ABC FGH

A. CD kinase needs cyclins to kick start the cell cycle progression. If made independent of cyclins they will continue the cell cycle progression and hence may lead to cancer.

B. RB protein is a tumour suppressor protein. It's highly phosporylated in cancer cells. It's dephosphorylation inhibits cancer by inhibiting EMT pathway. So any mutation that prevents dephosphorylation of RB protein may also lead to cancer.

C. Such mutation will prevent binding of p53, a tumor suppressor protein, thereby likely to cause cancer.

D. MDM 2 protein binding inhibits p53, thereby causing cancer. Any mutation that prevents this binding will suppress cancer.

E. As stated RB protein phosphorylation is associated with cancer. So a mutation that prevents phosphorylation prevents cancer.

Now RAS protein is proto- oncogenic. It is active in GDP mode and inactive in GTP mode. F and G mutations will lock the RAS protein in active mode causing cancer.

H. Protein p53 is activated by acetylation-phosphorylation mechanism to suppress cancer. Therefore mutations that prevent acetylation-phosphorylation prevent its activity thereby may lead to cancer.