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
Volume41
Issue number1
DOIs
Publication statusPublished - 29 Nov 2021

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