Evidence map›Paper›PMID 27346344›Full record

ArticleCell reports2016

GSK-3 and CK2 Kinases Converge on Timeless to Regulate the Master Clock.

Deniz Top, Emily Harms, Sheyum Syed, Eliza L Adams, Lino Saez

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Review
  3. Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Review
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  7. Coevolution ofiScience · 2025
    Article
  8. Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Alternative splicing ofbioRxiv : the preprint server for biology · 2024
    Article
  10. Review
  11. c-Jun N-terminal kinase signaling in aging.Frontiers in aging neuroscience · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Deniz TopLaboratory of Genetics, The Rockefeller University, 1230 York Avenue, Box 288, New York, NY 10065, USA. Electronic address: dtop@rockefeller.edu.
Emily HarmsLaboratory of Genetics, The Rockefeller University, 1230 York Avenue, Box 288, New York, NY 10065, USA.
Sheyum SyedDepartment of Physics, The University of Miami, 1320 Campo Sano Avenue, Coral Gables, FL 33146, USA.
Eliza L AdamsLaboratory of Genetics, The Rockefeller University, 1230 York Avenue, Box 288, New York, NY 10065, USA.
Lino SaezLaboratory of Genetics, The Rockefeller University, 1230 York Avenue, Box 288, New York, NY 10065, USA.
Rockefeller University · USUniversity of Miami · US

Funding

Molecular and Cellular Studies of Circadian RhythmsR37GM054339 · NIGMS · ROCKEFELLER UNIVERSITY · PI YOUNG, MICHAEL WARREN · 2009 to 2018
$3.8M
MOLECULAR AND CELLULAR STUDIES OF CIRCADIAN RHYTHMSR01GM054339 · NIGMS · ROCKEFELLER UNIVERSITY · PI YOUNG, MICHAEL WARREN · 1997 to 2008
$3.2M
NIGMS NIH HHS R01 GM054339NIGMS NIH HHS R37 GM054339
6 · The paper itself

Abstract

The molecular clock relies on a delayed negative feedback loop of transcriptional regulation to generate oscillating gene expression. Although the principal components of the clock are present in all circadian neurons, different neuronal clusters have varying effects on rhythmic behavior, suggesting that the clocks they house are differently regulated. Combining biochemical and genetic techniques in Drosophila, we identify a phosphorylation program native to the master pacemaker neurons that regulates the timing of nuclear accumulation of the Period/Timeless repressor complex. GSK-3/SGG binds and phosphorylates Period-bound Timeless, triggering a CK2-mediated phosphorylation cascade. Mutations that block the hierarchical phosphorylation of Timeless in vitro also delay nuclear accumulation in both tissue culture and in vivo and predictably change rhythmic behavior. This two-kinase phosphorylation cascade is anatomically restricted to the eight master pacemaker neurons, distinguishing the regulatory mechanism of the molecular clock within these neurons from the other clocks that cooperate to govern behavioral rhythmicity.

Indexed as

Circadian ClocksActive Transport, Cell NucleusAmino Acid SequenceAnimalsCasein Kinase IICell LineCell NucleusConserved SequenceDrosophila melanogasterDrosophila ProteinsGlycogen Synthase Kinase 3PhosphorylationProtein Processing, Post-TranslationalCasein Kinase IIDrosophila ProteinsGlycogen Synthase Kinase 3tim protein, Drosophila

Identifiers

PMID27346344
PMCPMC4945451
OpenAlexW2465199741

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.