Show simple item record

dc.contributor.authorKategaya, Lorna S.
dc.contributor.authorHilliard, Aisha
dc.contributor.authorZhang, Louying
dc.contributor.authorAsara, John M
dc.contributor.authorPtáček, Louis J.
dc.contributor.authorFu, Ying-Hui
dc.date.accessioned2013-02-21T20:35:02Z
dc.date.issued2012
dc.identifier.citationKategaya, Lorna S., Aisha Hilliard, Louying Zhang, John M. Asara, Louis J. Ptáček, and Ying-Hui Fu. 2012. Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock. PLoS ONE 7(2): e31987.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10318293
dc.description.abstractThroughout the day, clock proteins synchronize changes in animal physiology (e.g., wakefulness and appetite) with external cues (e.g., daylight and food). In vertebrates, both casein kinase 1 delta and epsilon (CK1\(\delta\) and CK1\(\epsilon\)) regulate these circadian changes by phosphorylating other core clock proteins. In addition, CK1 can regulate circadian-dependent transcription in a non-catalytic manner, however, the mechanism is unknown. Furthermore, the extent of functional redundancy between these closely related kinases is debated. To further advance knowledge about CK1\(\delta\) and CK1\(\epsilon\) mechanisms of action in the biological clock, we first carried out proteomic analysis of both kinases in human cells. Next, we tested interesting candidates in a cell-based circadian readout which resulted in the discovery of PROHIBITIN 2 (PHB2) as a modulator of period length. Decreasing the expression of PHB2 increases circadian-driven transcription, thus revealing PHB2 acts as an inhibitor in the molecular clock. While stable binding of PHB2 to either kinase was not detected, knocking down CK1\(\epsilon\) expression increases PHB2 protein levels and, unexpectedly, knocking down CK1\(\delta\) decreases PHB2 transcript levels. Thus, isolating CK1 protein complexes led to the identification of PHB2 as an inhibitor of circadian transcription. Furthermore, we show that CK1\(\delta\) and CK1\(\epsilon\) differentially regulate the expression of PHB2.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0031987en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288064/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectProteinsen_US
dc.subjectGeneticsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectProteomicsen_US
dc.titleCasein Kinase 1 Proteomics Reveal Prohibitin 2 Function in Molecular Clocken_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorAsara, John M
dc.date.available2013-02-21T20:35:02Z
dc.identifier.doi10.1371/journal.pone.0031987*
dash.contributor.affiliatedAsara, John


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record