The role of CDK 4/6 in cell cycle progression. CDK4/6–cyclin D1 complex is downstream of various mitogenic signals and suppressed by INK4 and CIP/KIP families. CDK4/6–cyclin D1 complex phosphorylates RB protein, which in turn releases E2F transcriptional factor and lead to G1 to S cell cycle progression. CDK, cyclin-dependent kinases; INK4, inhibitor of kinase 4; CIP/KIP, CDK interacting protein/kinase inhibitory protein; RB, retinoblastoma; G1, gap 1 cell cycle phase; S, synthesis cell cycle phase; ER, estrogen receptor; PR, progesterone receptor; AR, androgen receptor; MAPK, mitogen-activated protein kinase; JAK, Janus kinase; STAT, signal transducer and activator of transcription; PI3K, phosphoinositide 3-kinase