Question

Rb is such an important control point in the cell cycle that virtually all forms of cancer need to find some way around it. Describe 2 ways that a cancer cell could get around Rb inhibition.

Answer 1

Cyclin D CDK 4/6 is a protein complex which is required for cell to enter in cell cycle and catalyse phosphorylation of protein retinoblastoma (Rb) and inactivating it. Due to inactivation of protein retinoblastoma a transcriptional factor called E2F becomes active that stimulate transcription of Cyclin E CDK 2 complex as the cell approaches G1 to S transition of cell cycle.

Two ways that a cancer cell could get around Rb inhibition are:

• In phosphorylated form protein Rb is inactive and favors cell cycle progression and if due to some mutation it is unphosphorylated, Rb will become active and hence will prevent cell cycle progression.
• Loss of functional mutation in both copies of genes of protein Rb is associated with tumor (cancer) because normally protein Rb is tumor suppressor gene and is dominant in nature.