Phase portraits of the proliferation-quiescence decision.

Mammalian cells make the proliferation or quiescence decision at a specific point in the cell cycle called the restriction point, after which they become committed to proliferation and independent of growth factors for completion of mitosis. In the textbook view, this crucial transition occurs several hours after mitotic division (in the middle of G1 phase). In a Cell paper, Spencer et al. show that the restriction point should be defined not as a particular time point in G1 phase but in terms of the ON-OFF status of a bistable switch that emerges from the positive feedback in the CDK2-RB-E2F (cyclin-dependent kinase 2-retinoblastoma-E2F) interaction network.