Consider the ras oncogene. Ras proteins have GTPase activity, and their activity

Question

Consider the ras oncogene. Ras proteins have GTPase activity, and their activity is regulated by the presence of GTP or GDP. In the wildtype protein, growth-factor receptors with tyrosine kinase activity stimulate ras to exchange GDP with GTP, activating ras. Ras the activates the cystolic kinase (also an oncogene) craf. c-raf (also known as MAP kinase-kinase-kinase) is a kinase that then activates MAP kinase-kinase, which in turn activates MAP-kinase. MAP-kinase phosphorylates transcription factors in the nucleus. These transcription factors turn on genes required for cell division. After the appropriate genes have been transcribed, ras GTPase activity hydrolyses GTP, converting ras to its inative form. Consider the different conditions shown below. For each condition, describe what effect it would have on the cell and explain why.

A. Mutation leading to the deletion of CYs in ras caroxy terminus.

B. Mutation preventing hydrolysis of GTP by ras.

C. Addition of protein kinase inhibitors.

D. Mutation that prevents entry of MAP-kinase into the nucleus from the cytoplasm.

E. Mutation to E3 specific for ras that prevents complexing of ras with E3 and ubiquitin.

Explanation / Answer

Based on the given data,

A. Mutation leading to the deletion of CYs in ras caroxy terminus: I results the inactivation of the Ras protein, because the Carboxyl terminal of Ras has catalytic activity. Thus, Ras cannot hydrolyse GTP.

B. Mutation preventing hydrolysis of GTP by ras: It results the activity of Ras cannot be controlled by presence of GTP or GDP. Thus, it will lead to development of cancer.

C. Addition of protein kinase inhibitors: It results the inhibition of MAP kinase-kinase and MAP-kinase, thus the phosphorylation and activation of transcription factors in the nucleus cannot be allowed.

D. Mutation that prevents entry of MAP-kinase into the nucleus from the cytoplasm: It will results the inhibition of phosphorylation and activation of transcription factors in the nucleus. Thus, the genes cannot be expressed.

E. Mutation to E3 specific for ras that prevents complexing of ras with E3 and ubiquitin: It will also results the occurrence of cancer.

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