Skip to main content
Journal cover image

Origin of bistability underlying mammalian cell cycle entry.

Publication ,  Journal Article
Yao, G; Tan, C; West, M; Nevins, JR; You, L
Published in: Molecular systems biology
April 2011

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb-E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb-E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb-E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb-E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point.

Duke Scholars

Published In

Molecular systems biology

DOI

EISSN

1744-4292

ISSN

1744-4292

Publication Date

April 2011

Volume

7

Start / End Page

485

Related Subject Headings

  • Signal Transduction
  • Retinoblastoma Protein
  • Models, Biological
  • Mammals
  • Gene Regulatory Networks
  • Feedback, Physiological
  • E2F Transcription Factors
  • Cell Proliferation
  • Cell Differentiation
  • Cell Cycle Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yao, G., Tan, C., West, M., Nevins, J. R., & You, L. (2011). Origin of bistability underlying mammalian cell cycle entry. Molecular Systems Biology, 7, 485. https://doi.org/10.1038/msb.2011.19
Yao, Guang, Cheemeng Tan, Mike West, Joseph R. Nevins, and Lingchong You. “Origin of bistability underlying mammalian cell cycle entry.Molecular Systems Biology 7 (April 2011): 485. https://doi.org/10.1038/msb.2011.19.
Yao G, Tan C, West M, Nevins JR, You L. Origin of bistability underlying mammalian cell cycle entry. Molecular systems biology. 2011 Apr;7:485.
Yao, Guang, et al. “Origin of bistability underlying mammalian cell cycle entry.Molecular Systems Biology, vol. 7, Apr. 2011, p. 485. Epmc, doi:10.1038/msb.2011.19.
Yao G, Tan C, West M, Nevins JR, You L. Origin of bistability underlying mammalian cell cycle entry. Molecular systems biology. 2011 Apr;7:485.
Journal cover image

Published In

Molecular systems biology

DOI

EISSN

1744-4292

ISSN

1744-4292

Publication Date

April 2011

Volume

7

Start / End Page

485

Related Subject Headings

  • Signal Transduction
  • Retinoblastoma Protein
  • Models, Biological
  • Mammals
  • Gene Regulatory Networks
  • Feedback, Physiological
  • E2F Transcription Factors
  • Cell Proliferation
  • Cell Differentiation
  • Cell Cycle Proteins