How would a mutation that switches all the phosphorylated serines and threonines in Rb to alanine affect cell proliferation?

The mutation that converts all phosphorylated serines and threonines in the retinoblastoma protein (Rb) to alanine would significantly impact its function in regulating cell proliferation. Rb is a crucial tumor suppressor that acts as a gatekeeper at the G1/S transition of the cell cycle. When Rb is phosphorylated, it undergoes a conformational change that releases its grip on E2F transcription factors, which are essential for the transcription of genes required for DNA synthesis and the progression into S phase.

By replacing phosphorylated serines and threonines with alanine, the mutant form of Rb would be unable to undergo phosphorylation. This inability to be phosphorylated means that Rb would maintain its active, hypophosphorylated state. In this state, Rb binds tightly to E2F transcription factors, preventing their activity and consequently leading to a decrease in the transcription of genes necessary for entry into S phase.

As a result, the overall effect of this mutation is a reduction in cell proliferation since the downstream processes that promote cell cycle progression and DNA synthesis would be inhibited. This illustrates the critical role that post-translational modifications, such as phosphorylation, play in regulating cellular processes and how alterations in these modifications