 When they bind to CDK4 and CDK6, they induce an allosteric change that leads to the formation of CDK-INK4 complexes rather than CDK-cyclin complexes.This leads to an inhibition of retinoblastoma (Rb) phosphorylation downstream.Therefore, the expression of p15INK4b or p16INK4A keeps the Rb-family proteins hypophosphorylated.