Control of the Restriction Point by Rb and p21

Significance The canonical Restriction Point model suggests that cells are born into a state in which they are uncommitted to the cell cycle, but will activate cyclin-dependent kinase 2 and cross the Restriction Point several hours later if sufficient nutrients are available. However, recent single-cell studies have challenged aspects of this model. This work examines the Restriction Point in cancerous and noncancerous cells and shows that, in six cases tested, the cell populations split such that only a subset of cells is born into a pre-Restriction Point state, while the remainder immediately commits to another cell cycle. This shows that even cancer cells can experience significant heterogeneity in this cell fate decision, which may be exploitable for therapeutic gain.