CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis

Wong, D. C. S.; Seinkmane, E.; Stangherlin, A.; Zeng, A.; Rzechorzek, N. M.; Beale, A. D.; Day, J.; Reed, M.; Peak-Chew, S. Y.; Putker, M.; O'Neill, J. S.

doi:10.1101/2020.05.16.099556

bioRxiv · 10.1101/2020.05.16.099556

CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis

Wong, D. C. S.·Seinkmane, E.·Stangherlin, A.·Zeng, A.·Rzechorzek, N. M.·Beale, A. D.·Day, J.·Reed, M.·Peak-Chew, S. Y.·Putker, M.·O'Neill, J. S.

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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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Wong, D. C. S., Seinkmane, E., Stangherlin, A., Zeng, A., Rzechorzek, N. M., Beale, A. D., Day, J., Reed, M., Peak-Chew, S. Y., Putker, M., O'Neill, J. S.. 2020-05-16. CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis. https://doi.org/10.1101/2020.05.16.099556

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