ArticleMolecular systems biology2009
Protein sequestration generates a flexible ultrasensitive response in a genetic network.
Article in Molecular systems biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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129 citing papers in PubMed, 242 citations in OpenAlex.
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- Chromosome segregation synchrony inbioRxiv : the preprint server for biology · 2026Article
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Circadian clock model with sequestration repression motif: existence of periodic orbits and entrainment properties.Interface focus · 2025Article
- Pattern recognition in living cells through the lens of machine learning.Open biology · 2025Review
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- Engineering Sequestration-Based Biomolecular Classifiers with Shared Resources.ACS synthetic biology · 2024Article
- High-resolution and programmable RNA-IN and RNA-OUT genetic circuit in living mammalian cells.Nature communications · 2024Article
- Principles of Computation by Competitive Protein Dimerization Networks.bioRxiv : the preprint server for biology · 2024Article
- Anti-windup strategies for biomolecular control systems facilitated by model reduction theory for sequestration networks.Science advances · 2024Article
- A robust ultrasensitive transcriptional switch in noisy cellular environments.NPJ systems biology and applications · 2024Article
- Design patterns of biological cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- The motility-matrix production switch inJournal of bacteriology · 2024Article
- Transcription factor competition facilitates self-sustained oscillations in single gene genetic circuits.PLoS computational biology · 2023Article
- Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.Journal of biomedical science · 2023Review
- A General Approach for the Modelling of Negative Feedback Physiological Control Systems.Bioengineering (Basel, Switzerland) · 2023Article
- Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sites.PLoS computational biology · 2022Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ultrasensitive responses are crucial for cellular regulation. Protein sequestration, where an active protein is bound in an inactive complex by an inhibitor, can potentially generate ultrasensitivity. Here, in a synthetic genetic circuit in budding yeast, we show that sequestration of a basic leucine zipper transcription factor by a dominant-negative inhibitor converts a graded transcriptional response into a sharply ultrasensitive response, with apparent Hill coefficients up to 12. A simple quantitative model for this genetic network shows that both the threshold and the degree of ultrasensitivity depend upon the abundance of the inhibitor, exactly as we observed experimentally. The abundance of the inhibitor can be altered by simple mutation; thus, ultrasensitive responses mediated by protein sequestration are easily tuneable. Gene duplication of regulatory homodimers and loss-of-function mutations can create dominant negatives that sequester and inactivate the original regulator. The generation of flexible ultrasensitive responses is an unappreciated adaptive advantage that could explain the frequent evolutionary emergence of dominant negatives.
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