Letter abstract
Nature Cell Biology 10, 476 - 482 (2008)
Published online: 23 March 2008 | doi:10.1038/ncb1711
A bistable Rb–E2F switch underlies the restriction point
Guang Yao1,2, Tae Jun Lee3, Seiichi Mori1,2, Joseph R. Nevins1,2 & Lingchong You1,3
The restriction point (R-point) marks the critical event when a mammalian cell commits to proliferation and becomes independent of growth stimulation. It is fundamental for normal differentiation and tissue homeostasis, and seems to be dysregulated in virtually all cancers1, 2. Although the R-point has been linked to various activities involved in the regulation of G1–S transition of the mammalian cell cycle2, 3, 4, 5, 6, the underlying mechanism remains unclear1, 7. Using single-cell measurements, we show here that the Rb–E2F pathway functions as a bistable switch to convert graded serum inputs into all-or-none E2F responses. Once turned ON by sufficient serum stimulation, E2F can memorize and maintain this ON state independently of continuous serum stimulation. We further show that, at critical concentrations and duration of serum stimulation, bistable E2F activation correlates directly with the ability of a cell to traverse the R-point.
- Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Correspondence to: Lingchong You1,3 e-mail: you@duke.edu
Correspondence to: Joseph R. Nevins1,2 e-mail: j.nevins@duke.edu
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