structural:expansion, information:extraction
Control of pRb function by phosphorylation

This function of un-phosphorylated pRb gives rise to a hypothesis for the lack of cell cycle control in cancerous cells: Deregulation of Cyclin D - Cdk 4/6 phosphorylates un-phosphorylated pRb in senescent cells to mono-phosphorylated pRb, causing them to enter G1. The mechanism of the switch for Cyclin E activation is not known, but one hypothesis is that it is a metabolic sensor. Mono-phosphorylated pRb induces an increase in metabolism, so the accumulation of mono-phosphorylated pRb in previously G0 cells then causes hyper-phosphorylation and mitotic entry. Since any un-phosphorylated pRb is immediately phosphorylated, the cell is then unable to exit the cell cycle, resulting in continuous division.