The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3β
Open accessAbstract
The circadian clock controls daily oscillations of gene expression at the cellular level. We report the development of a high-throughput circadian functional assay system that consists of luminescent reporter cells, screening automation, and a data analysis pipeline. We applied this system to further dissect the molecular mechanisms underlying the mammalian circadian clock using a chemical biology approach. We analyzed the effect of 1,280 pharmacologically active compounds with diverse structures on the circadian period length that is indicative of the core clock mechanism. Our screening paradigm identified many compounds previously known to change the circadian period or phase, demonstrating the validity of the assay system. Furthermore, we found that small molecule inhibitors of glycogen synthase kinase 3 (GSK-3) consistently caused a strong short period phenotype in contrast to the well-known period lengthening by lithium, another presumed GSK-3 inhibitor. siRNA-mediated knockdown of GSK-3β also caused a short period, confirming the phenotype obtained with the small molecule inhibitors. These results clarify the role of GSK-3β in the period regulation of the mammalian clockworks and highlight the effectiveness of chemical biology in exploring unidentified mechanisms of the circadian clock.
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Cites
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“In contrast, roscovitine, that inhibits CDK but not GSK-3 (27), caused a long period phenotype (Table 1).”
BackgroundInfluentialFunctional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome
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A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock
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Cited by
Molecular mechanisms and physiological importance of circadian rhythms
Patke, A., Young, M. W., & Axelrod, S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0179-2 · Cited by 1,388
Circadian rhythms persist without transcription in a eukaryote
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Circadian clock control of endocrine factors
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GSK-3: Functional Insights from Cell Biology and Animal Models
Kaidanovich-Beilin, O., & Woodgett, J. R. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00040 · Cited by 485
Clocks not winding down: unravelling circadian networks
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Self-citation
Metadata
- Authors
- Hirota, T., Lewis, W. G., Liu, A. C., Lee, J. W., Schultz, P. G., & Kay, S. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-12-30
- Volume
- 105
- Issue
- 52
- Pages
- 20746-20751
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1991080086
- Cited by
- 283
- References
- 6
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Hirota, T., Lewis, W. G., Liu, A. C., Lee, J. W., Schultz, P. G., & Kay, S. A. (2008). A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3β. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0811410106
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