Explain in detail how p53 and Rb can contribute to the onset of malignancy.

Answer: Rb is the protein product of the retinoblastoma susceptibility gene, which predisposes individuals to retinoblastomas and other tumors when only one functional copy is present. Rb is present throughout the cell cycle. Phosphorylations vary with each cell-cycle phase. In its hypophosphorylated (active) state, Rb has antiproliferative effects, inhibiting cell cycling. It does this by inhibiting transcription factors required for the transcription of genes needed for cell proliferation, rendering them nonfunctional. Hyperphosphorylation, on the other hand, neutralizes (inactivates) the Rb protein, thus promoting cell cycle division.
P53 acts as a molecular policeman; it monitors the integrity of the genome. It can activate and inhibit gene expression depending on the target gene. It is activated in response to DNA breakage,
and slows cell-cycle division to initiate DNA repair or apoptosis. It functions as a tumor suppressor gene, and it is the most common mutated gene in tumors.