Evidence map›Paper›PMID 26562092›Full record

ArticlePLoS biology2015

CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock.

Teruya Tamaru, Mitsuru Hattori, Kousuke Honda, Yasukazu Nakahata, Paolo Sassone-Corsi, Gijsbertus T J van der Horst, Takeaki Ozawa, Ken Takamatsu

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  3. Article
  4. Review
  5. Circadian Control of Protein Synthesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Introduction to the Clock System.Advances in experimental medicine and biology · 2021
    Article
  14. Review
  15. Circadian regulation of c-MYC in mice.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Article
  17. Review
  18. Circadian Clock Regulation on Lipid Metabolism and Metabolic Diseases.Advances in experimental medicine and biology · 2020
    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

8 authors at 5 institutions in 3 countries.

Teruya TamaruDepartment of Physiology and Advanced Research Center for Medical Science, Toho University School of Medicine, Tokyo, Japan.
Mitsuru HattoriDepartment of Chemistry, The University of Tokyo, Tokyo, Japan.
Kousuke HondaDepartment of Chemistry, The University of Tokyo, Tokyo, Japan.
Yasukazu NakahataLaboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
Paolo Sassone-CorsiDepartment of Biological Chemistry, University of California, Irvine, Irvine, California, United States of America.
Gijsbertus T J van der HorstDepartment of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Takeaki OzawaDepartment of Chemistry, The University of Tokyo, Tokyo, Japan.
Ken TakamatsuDepartment of Physiology and Advanced Research Center for Medical Science, Toho University School of Medicine, Tokyo, Japan.
The University of Tokyo · JPToho University · JPErasmus MC · NLNara Institute of Science and Technology · JPUniversity of California, Irvine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

Indexed as

Circadian ClocksProtein Processing, Post-TranslationalAnimalsARNTL Transcription FactorsCasein Kinase IICell LineCells, CulturedCryptochromesEmbryo, MammalianHumansMiceMice, KnockoutMice, TransgenicMutationPhosphorylationProtein Interaction Domains and MotifsARNTL Transcription FactorsBmal1 protein, mouseCasein Kinase IICry1 protein, mouseCry2 protein, mouseCryptochromesCSNK2A1 protein, humanRecombinant Fusion ProteinsRecombinant Proteins

Identifiers

PMID26562092
PMCPMC4642984
OpenAlexW2179642256

What OpenQuestion holds

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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.