Evidence map›Paper›PMID 30875610›Full record

ArticleiScience2019

The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1α.

Elitsa Y Dimova, Mirza Jakupovic, Kateryna Kubaichuk, Daniela Mennerich, Tabughang Franklin Chi, Filippo Tamanini, Małgorzata Oklejewicz, Jens Hänig, Nadiya Byts, Kari A Mäkelä and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 62 citations in OpenAlex.

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  7. Circadian clock and cancer.Military Medical Research · 2026
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  8. HIF1α mediates circadian regulation of skeletal muscle metabolism and substrate preference in response to time-of-day exercise.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

15 authors at 4 institutions in 3 countries.

Elitsa Y DimovaFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland. Electronic address: elitsa.dimova@oulu.fi.
Mirza JakupovicDepartment of Biochemistry, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Kateryna KubaichukFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland.
Daniela MennerichFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland.
Tabughang Franklin ChiFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland.
Filippo TamaniniDepartment of Molecular Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.
Małgorzata OklejewiczDepartment of Molecular Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.
Jens HänigNovartis Pharma GmbH, 97082 Würzburg, Germany.
Nadiya BytsFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland.
Kari A MäkeläBiocenter Oulu, Department of Physiology, University of Oulu, 90014 Oulu, Finland.
Karl-Heinz HerzigBiocenter Oulu, Department of Physiology, University of Oulu, 90014 Oulu, Finland.
Peppi KoivunenFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland.
Ines ChavesDepartment of Molecular Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.
Gijsbertus van der HorstDepartment of Molecular Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.
Thomas KietzmannFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland. Electronic address: thomas.kietzmann@oulu.fi.
University of Oulu · FIErasmus MC · NLNovartis (Germany) · DEUniversity of Kaiserslautern · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor (HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1α via its tail region. Subsequently, CRY1 reduces HIF-1α half-life and binding of HIFs to target gene promoters. This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout. Altogether, our study provides a mechanistic explanation for genetic association studies linking a disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis.

Indexed as

BiochemistryBiological SciencesCell BiologyMolecular Biology

Identifiers

PMID30875610
PMCPMC6416729
OpenAlexW2919465720

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.