CRYPTOCHROMES promote daily protein homeostasis

David C S Wong, Estere Seinkmane, Aiwei Zeng, Alessandra Stangherlin, Nina Rzechorzek, Andrew D Beale, Jason Day, Martin Reed, Sew Y Peak-Chew, Christine T Styles, Rachel S Edgar, Marrit Putker, John S O'Neill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 used quantitative mass spectrometry to compare wild-type and CRY-deficient fibroblasts under constant conditions. In CRY-deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild-type controls. Most strikingly, the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY-deficient cells. This proteome imbalance in CRY-deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide-ranging phenotypes of CRY-deficient mice. Rather than generating large-scale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post-translational functions of CRY proteins ultimately act to maintain protein and osmotic homeostasis against daily perturbation.
Original languageEnglish
Article numbere108883
Number of pages23
JournalEMBO Journal
Issue number1
Publication statusPublished - 29 Nov 2021


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