ArticleNature cell biology2013
The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch.
Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 150 citations in OpenAlex.
- Differential roles for the spindle assembly checkpoint in error surveillance and mitotic timing.The EMBO journal · 2026Article
- Energy-precision trade-off in mitotic oscillators revealed by ATP modulation in artificial cells.bioRxiv : the preprint server for biology · 2026Article
- CDK1 Signaling in Cancer Treatment: Advances in AI-based Strategies and Tools for New Cancer Drug Discovery.Combinatorial chemistry & high throughput screening · 2026Article
- Synthetic Cell-Based Approaches to Dissect Autonomous Cellular Oscillators: Recent Applications on the Cell Cycle.Advances in experimental medicine and biology · 2026Review
- Article
- Mechanistic origins of temperature scaling in the early embryonic cell cycle.Nature communications · 2025Article
- A novel pathway for stemness propagation and chemoresistance in non-small cell lung cancer via phosphorylated PKM2-loaded small extracellular vesicles.Theranostics · 2025Article
- Review
- Spatial heterogeneity accelerates phase-to-trigger wave transitions in frog egg extracts.Nature communications · 2024Article
- Entrainment and multi-stability of the p53 oscillator in human cells.Cell systems · 2024Article
- Abrogation of the G2/M checkpoint as a chemosensitization approach for alkylating agents.Neuro-oncology · 2024Article
- The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.Open biology · 2024Article
- Comprehensive Parameter Space Mapping of Cell Cycle Dynamics under Network Perturbations.ACS synthetic biology · 2024Article
- CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification.JCI insight · 2024Article
- Mitotic waves in frog egg extracts: Transition from phase waves to trigger waves.bioRxiv : the preprint server for biology · 2024Article
- A model of replicating coupled oscillators generates naturally occurring cell networks.Development (Cambridge, England) · 2023Article
- Transcription factor competition facilitates self-sustained oscillations in single gene genetic circuits.PLoS computational biology · 2023Article
- The ups and downs of biological oscillators: a comparison of time-delayed negative feedback mechanisms.Journal of the Royal Society, Interface · 2023Article
- Cell cycle oscillations driven by two interlinked bistable switches.Molecular biology of the cell · 2023Article
- Nuclear-cytoplasmic compartmentalization of cyclin B1-Cdk1 promotes robust timing of mitotic events.Cell reports · 2022Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Despite the complexity and variety of biological oscillators, their core design invariably includes an essential negative feedback loop. In the Xenopus laevis embryonic cell cycle oscillator, this loop consists of the kinase cyclin B-Cdk1 and the ubiquitin ligase APC/C(Cdc20); active Cdk1 activates APC/C(Cdc20), which then brings about cyclin B degradation and inactivates Cdk1. Here we ask how this negative feedback loop functions quantitatively, with the aim of understanding what mechanisms keep the Cdk1-APC/C(Cdc20) system from settling into a stable steady state with intermediate levels of Cdk1 and APC/C(Cdc20) activity. We found that the system operates as a time-delayed, digital switch, with a time lag of ∼ 15 min between Cdk1 and APC/C(Cdc20) activation and a tremendously high degree of ultrasensitivity (n(H)≈17). Computational modelling shows how these attributes contribute to the generation of robust, clock-like oscillations. Principles uncovered here may also apply to other activator-repressor oscillators and help in designing robust synthetic clocks.
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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.