Figure 7.

Hysteresis in the proliferation switch in mammalian cells. (From Yao et al. [41].) (a) The three proteins RB, E2F and CycE are involved in a positive feedback loop (−+−), which creates a bistable switch for the activity of CycE-dependent kinase (the signal that starts a sequence of events leading to DNA synthesis and mitosis in mammalian cells). (b) The level of CycD in the cell determines whether CycE-dependent kinase activity is low (non-proliferating state) or high (proliferating state). CycD concentration responds to external signals from growth factors, extracellular matrix attachments and cell–cell contacts. (Online version in colour.)