Describe the P16INK4a/CDK4/RB1 pathway in healthy cells.

Rb protein and E2F are bound in a complex. CDK4/6 and cyclin D when bound, partially phosphorylate the RB/E2F complex, causing the release of E2F, activating both the G1 - S phase transition in the cell cycle and P16INK4a tumor suppressor. P16INK4a causes the recombination of E2F and RB to limit further cell proliferation.