01The cell cycle at a glance
Every dividing cell moves through four phases: G1 (growth and decision-making), S (DNA synthesis), G2 (preparation) and M (mitosis). Cells that stop dividing exit into G0, a resting state where most of your adult cells — neurons, muscle fibers, many liver cells — spend their lives.
The cycle isn't a timer. It's a series of molecular switches that flip only when conditions are right. Cancer is, at its core, a disease of switches stuck in the 'on' position.
02Cyclin–CDK partners
The motors are cyclin-dependent kinases (CDKs). A CDK is inactive by itself; it must bind a cyclin partner. Cyclin levels rise and fall each cycle (that's where the name comes from), while CDK levels stay fairly constant. Cyclin D–CDK4/6 drives early G1, cyclin E–CDK2 pushes the G1/S transition, cyclin A–CDK2 runs S phase, and cyclin B–CDK1 triggers mitosis.
Full activation also needs an activating phosphorylation by CAK (CDK-activating kinase) and removal of inhibitory phosphates by Cdc25 phosphatases. Cells then destroy cyclins by ubiquitination so the cycle can reset.
03The brakes: CDK inhibitors
Two families of CDK inhibitors (CKIs) keep the engine in check. The INK4 family (p16INK4a, p15) blocks CDK4/6 specifically. The CIP/KIP family (p21, p27, p57) blocks a broader range of cyclin–CDK complexes.
Clinically, this matters: p16 is one of the most frequently deleted genes in human cancer, and drugs like palbociclib — CDK4/6 inhibitors — are now standard treatment for hormone-receptor-positive breast cancer. They do what p16 used to.