CRYPTOCHROMES promote daily protein homeostasis.
EMBO J
; 41(1): e108883, 2022 01 04.
Article
em En
| MEDLINE
| ID: mdl-34842284
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 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ritmo Circadiano
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Criptocromos
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Proteostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article