CRYPTOCHROMES promote daily protein homeostasis.

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cam.issuedOnline2021-11-29
dc.contributor.authorWong, David CS
dc.contributor.authorSeinkmane, Estere
dc.contributor.authorZeng, Aiwei
dc.contributor.authorStangherlin, Alessandra
dc.contributor.authorRzechorzek, Nina M
dc.contributor.authorBeale, Andrew D
dc.contributor.authorDay, Jason
dc.contributor.authorReed, Martin
dc.contributor.authorPeak-Chew, Sew Y
dc.contributor.authorStyles, Christine T
dc.contributor.authorEdgar, Rachel S
dc.contributor.authorPutker, Marrit
dc.contributor.authorO'Neill, John S
dc.contributor.orcidWong, David CS [0000-0002-1712-9527]
dc.contributor.orcidSeinkmane, Estere [0000-0002-3636-4709]
dc.contributor.orcidZeng, Aiwei [0000-0003-0354-2529]
dc.contributor.orcidStangherlin, Alessandra [0000-0001-7296-1183]
dc.contributor.orcidRzechorzek, Nina M [0000-0003-3209-5019]
dc.contributor.orcidBeale, Andrew D [0000-0002-2051-0919]
dc.contributor.orcidDay, Jason [0000-0002-3078-0963]
dc.contributor.orcidPeak-Chew, Sew Y [0000-0002-7602-6384]
dc.contributor.orcidStyles, Christine T [0000-0001-7337-2540]
dc.contributor.orcidEdgar, Rachel S [0000-0002-3348-0851]
dc.contributor.orcidPutker, Marrit [0000-0001-9290-408X]
dc.contributor.orcidO'Neill, John S [0000-0003-2204-6096]
dc.date.accessioned2021-12-15T11:10:22Z
dc.date.available2021-12-15T11:10:22Z
dc.date.issued2022-01-04
dc.date.submitted2021-06-03
dc.date.updated2021-12-15T11:10:22Z
dc.description.abstractThe 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.
dc.identifier.doi10.17863/CAM.78913
dc.identifier.eissn1460-2075
dc.identifier.issn0261-4189
dc.identifier.otherembj2021108883
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331459
dc.languageen
dc.publisherEMBO
dc.publisher.urlhttp://dx.doi.org/10.15252/embj.2021108883
dc.subjectCRYPTOCHROME
dc.subjectcircadian rhythm
dc.subjectclock mutant
dc.subjectprotein homeostasis
dc.subjectproteotoxic stress
dc.subjectAnimals
dc.subjectCircadian Rhythm
dc.subjectCryptochromes
dc.subjectIon Transport
dc.subjectMice
dc.subjectPhosphoproteins
dc.subjectProteasome Endopeptidase Complex
dc.subjectProteome
dc.subjectProteomics
dc.subjectProteostasis
dc.subjectReproducibility of Results
dc.subjectStress, Physiological
dc.subjectTime Factors
dc.titleCRYPTOCHROMES promote daily protein homeostasis.
dc.typeArticle
dcterms.dateAccepted2021-11-09
prism.publicationNameEMBO J
pubs.funder-project-idWellcome Trust (093734/Z/10/Z)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.versionofrecord10.15252/embj.2021108883
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