ArticleMolecular systems biology2011
Origin of bistability underlying mammalian cell cycle entry.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Design principles for robust multistability in coupled feedforward-feedback regulatory circuits.NPJ systems biology and applications · 2026Article
- Cell cycle criticality as a mechanism for robust cell population control.Molecular systems biology · 2026Article
- DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.Cell reports · 2025Article
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- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.bioRxiv : the preprint server for biology · 2025Article
- Network topology and interaction logic determine states it supports.NPJ systems biology and applications · 2024Review
- Quiescence-Origin Senescence: A New Paradigm in Cellular Aging.Biomedicines · 2024Article
- The art of modeling gene regulatory circuits.NPJ systems biology and applications · 2024Article
- Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales.The Biochemical journal · 2023Review
- Constructing maps between distinct cell fates and parametric conditions by systematic perturbations.Bioinformatics (Oxford, England) · 2023Article
- The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development.Communications biology · 2023Article
- Daughter cell fate choice instructed preemptively by mother cells facing nutrient limitation.iScience · 2023Article
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- Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.iScience · 2023Article
- Mathematically Modeling the Effect of Endocrine and Cdk4/6 Inhibitor Therapies on Breast Cancer Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Extracellular Fluid Flow Induces Shallow Quiescence Through Physical and Biochemical Cues.Frontiers in cell and developmental biology · 2022Article
- The partition representation of enzymatic reaction networks and its application for searching bi-stable reaction systems.PloS one · 2022Article
- Effects of noise and time delay on E2F's expression level in a bistable Rb-E2F gene's regulatory network.IET systems biology · 2021Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.