ArticleCell2011
NEMO/NLK phosphorylates PERIOD to initiate a time-delay phosphorylation circuit that sets circadian clock speed.
Article in Cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 109 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 181 citations in OpenAlex.
- Oligomerization of PER2 as a dynamic mode of regulation of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Review
- Neuropeptide dynamics coordinate layered plasticity mechanisms adaptingScience advances · 2025Article
- Article
- A wrinkle in timers: evolutionary rewiring of conserved biological timekeepers.Trends in biochemical sciences · 2025Review
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period.Molecular cell · 2023Article
- Differential regulation of phosphorylation, structure, and stability of circadian clock protein FRQ isoforms.The Journal of biological chemistry · 2023Article
- Functional analysis of 110 phosphorylation sites on the circadian clock protein FRQ identifies clusters determining period length and temperature compensation.G3 (Bethesda, Md.) · 2023Article
- Endogenous circadian reporters reveal functional differences ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- Regulation of PDF receptor signaling controlling daily locomotor rhythms in Drosophila.PLoS genetics · 2022Article
- Casein kinase rolls the dice in clocks from bread mold to humans.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Casein kinase 1 and disordered clock proteins form functionally equivalent, phospho-based circadian modules in fungi and mammals.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Systematic modeling-driven experiments identify distinct molecular clockworks underlying hierarchically organized pacemaker neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Time-course RNASeq of Camponotus floridanus forager and nurse ant brains indicate links between plasticity in the biological clock and behavioral division of labor.BMC genomics · 2022Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The speed of circadian clocks in animals is tightly linked to complex phosphorylation programs that drive daily cycles in the levels of PERIOD (PER) proteins. Using Drosophila, we identify a time-delay circuit based on hierarchical phosphorylation that controls the daily downswing in PER abundance. Phosphorylation by the NEMO/NLK kinase at the "per-short" domain on PER stimulates phosphorylation by DOUBLETIME (DBT/CK1δ/ɛ) at several nearby sites. This multisite phosphorylation operates in a spatially oriented and graded manner to delay progressive phosphorylation by DBT at other more distal sites on PER, including those required for recognition by the F box protein SLIMB/β-TrCP and proteasomal degradation. Highly phosphorylated PER has a more open structure, suggesting that progressive increases in global phosphorylation contribute to the timing mechanism by slowly increasing PER susceptibility to degradation. Our findings identify NEMO as a clock kinase and demonstrate that long-range interactions between functionally distinct phospho-clusters collaborate to set clock speed.
Indexed as
Identifiers
What OpenQuestion holds
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.