Question

Which of the following alterations would likely contribute to the formation of a cancerous somatic cell?

A.Mutations in cyclin-dependent kinase genes that made the catalytic activity of the kinases cyclin-independent.
B. A mutation in the Mdm2 gene that eliminated the ability of the MDM2 protein to bind to p53.
C.A mutation that inactivated expression of the gene that encoded the protein that de-phosphorylated the RB protein.
D. A mutation in the Ras gene that eliminated the GTPase activity of the RAS protein.
E. Mutations in the p53 gene that eliminated the sites of phosphorylation and acetylation on the p53 protein.
F. A mutation in the Ras gene that generated a RAS protein that would not release bound GDP.
G. A mutation in the Retinoblastoma (Rb) gene that eliminated the phosphorylation site on the RB protein.
H.A mutation in the p53 transcription factor binding site near the Bax gene promoter that eliminated p53 binding.

Answer 1

All the alterations which lead to formation of cancerous somatic cells are . A, C, D, E, H ARE CORRECT

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

CDK act at various step in cell cycle and carry various phases in to next phase. Their activity is regulated by cyclins . If there is mutation in kinase and now they are not regulated by cyclins . In this case cell will always divide and in a abnormal or unregulated way thus increase chances of cancer formation.

C mutation that inactivated expression of the gene that encoded the protein that de-phosphorylated the RB protein. Rb hold transcription factor E2F , required for G1 to s transition. In presence of growth signal the is phosphorylation of Rb and this release E2F and cause G1 to S transition. This effect is readily stopped by dephosphorylation of RB. But if there us inactivation of gene that cause de phosphorylation, than RB will remain phosphorylated and E2F will be released and cause unchecked G1 to S transition. This increase risk of cancer formation.
D. A mutation in the Ras gene that eliminated the GTPase activity of the RAS protein. During signal transduction, RAS GDP replaced by GTP and transmit signal. As signal removed Ras GTPase activity hydrolyzed GTP and lead to signal termination. But if this GTPase activity lost than GTP will always present in binding with Ras always provide growth signal and excessive cell division and cancer formation.
E. Mutations in the p53 gene that eliminated the sites of phosphorylation and acetylation on the p53 protein. Upon DNA damage, various protein get activated which phosphorylate p53 and their activation. This p53 is master regulator which mediate further all the response. So if we remove these phosphorylated sites than p53 will not get activated and not participate in correcting the damage and causs cancer formation

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

P53 Bax pathway play an important role as tumor supressor. If p53 will not bind to bax promoter than no bax. And no tumor supressor function and increase chances of cancer formation.  

F and H are the opposite of above explained example, they prevent the chances of tumor formation.  

B acy as negative regulator of p53. If we remove mdm 2 than p53 will show it's function and will supress tumor formation.