CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis
Open accessPreprint — published as 10.15252/embj.2021108883 · Paper page
Abstract
The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we compared the circadian proteome and phosphoproteome of wild type and CRY-deficient fibroblast cells. Strikingly, CRY-deficient cells showed a two-fold increase in circadian-regulated proteins, phosphopeptides, and K + transport. This was accompanied by extensive remodelling of the cellular proteome overall, including reduced phosphatase and proteasome subunit expression. These adaptations rendered CRY-deficient cells more sensitive to stress, which may account for their reduced circadian robustness and contribute to the wide-ranging phenotypes of CRY-deficient mice. We suggest that CRY ultimately functions to suppress, rather than generate, daily rhythms in cellular protein abundance, thereby maintaining protein and osmotic homeostasis.
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
MECP2 disorders: from the clinic to mice and back
Lombardi, L. M., Baker, S. A., & Zoghbi, H. Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78167 · Cited by 221 · see citing works
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- Authors
- Wong, D. C. S., Seinkmane, E., Stangherlin, A., Zeng, A., Rzechorzek, N. M., Beale, A. D., Day, J., Reed, M., Chew, S. P., Styles, C. T., Edgar, R. S., Putker, M., & O’Neill, J. S.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- Imperial College London (GB)
- ORCID
- Venue
- The EMBO Journal
- Publisher
- openRxiv
- Published
- 2020-05-16
- Volume
- 41
- Issue
- 1
- Pages
- e108883-e108883
- ISSN
- 0261-4189 (ISSN-L)
- PMC
- PMC8724739
- OpenAlex
- W3214833691
- Cited by
- 30
- References
- 2
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 7 · 2021: 8 · 2020: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Funders
- AstraZeneca
- Wellcome Trust (093734, 093734/Z/10/Z)
- EMBO (ALTF‐654‐2014)
- KWF Kankerbestrijding (BUIT‐2014‐6637)
- Medical Research Council (MC_EX_MR/S022023/1, MR/S022023/1, 1857414, MC_UP_1201/4)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- cryptochrome, circadian clock, proteostasis, osmotic balance, proteotoxic stress, phosphopeptides, potassium homeostasis
- MeSH terms
- Proteostasis, Animals, Circadian Rhythm, Phosphoproteins, Stress, Physiological, Time Factors, Reproducibility of Results, Ion Transport, Proteome, Proteomics, Proteasome Endopeptidase Complex, Mice, Cryptochromes
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