Question

A tumor cell with a mutation in Rb can divide in the absence of extracellular signals.

A. If the Rb mutation is responsible for the increased cell division, is it likely that Rb is always active or always inactive? Explain your reasoning.

B. Which of the following molecules would be likely to block division of these tumor cells? Select all that would block division in cells with this Rb mutation.

       a. An inhibitor of Ras GEF

   b. A MAPK inhibitor

       c. An inhibitor of the G1 checkpoint Cdk

   d. An inhibitor of E2F (transcription factor regulated by Rb)

   e. An inhibitor of DNA polymerase

C. Explain why the choice/one choice in part B would block division of cells expressing this Rb mutant.

D. Explain why one of the choices in part B that you did NOT select would NOT block cell division in cell expressing this Rb mutant.

Answer 1

A. If the Rb mutation is responsible for the increased cell division, is it likely that Rb is always inactive.

In normal cells, mitogens activate the MAP kinase pathway and increase the G1- CDK activity. G1-CDK increases the transcription of gene regulatory factors ( e.g E2F). Retinoblastoma in its active form inhibits the activation of this gene regulatory factors whereas when retinoblastoma is phosphorylated it can't inhibit. So, if retinoblastoma is mutated then it can't inhibit the activation of E2F.

B. Answers are options b,c,d and e.

C. As I have already mentioned that mitogens activate the MAP kinase pathway, thus an inhibitor of this pathway will not allow the G1-Cdk to become activated.

An inhibitor of G1- Cdk will inhibits it to activate E2F.

An inhibitor of E2F will inhibits E2F to activate the G1-S cyclones.

An inhibitor of DNA polymerase will not allow the DNA to replicate. Thus, cells will not multiply. The retinoblastoma acts prior to S phase. Thus all the inhibitors which block the transition of cell from G1 phase to S phase, will block cell cycle.

D. An inhibitor of Ras-GEF will not halt the cell cycle.

Although MAP kinase pathway is activated by Ras, it can also be activated by some other pathways. So, even if inhibitor of Ras-GEF may inhibit MAP kinase pathway, due to activation of some other pathways MAP kinase can be activated