A bistable Rb-E2F switch underlies the restriction point.

Published

Journal Article

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 cancers. Although the R-point has been linked to various activities involved in the regulation of G1-S transition of the mammalian cell cycle, the underlying mechanism remains unclear. 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.

Full Text

Duke Authors

Cited Authors

  • Yao, G; Lee, TJ; Mori, S; Nevins, JR; You, L

Published Date

  • April 2008

Published In

Volume / Issue

  • 10 / 4

Start / End Page

  • 476 - 482

PubMed ID

  • 18364697

Pubmed Central ID

  • 18364697

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

International Standard Serial Number (ISSN)

  • 1465-7392

Digital Object Identifier (DOI)

  • 10.1038/ncb1711

Language

  • eng