We have previously found in kinetic analyses from highly synchronized normal cells and p16-deficient cancer cells that cyclin D:Cdk4/6 is constitutively active throughout early G1 phase at the same time when Rb is repressing E2F target genes (Ezhevsky et al., 1997, 2001; Haberichter et al., 2007). The gene discussed is CDK4; the disease is cancer.