{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T06:52:29Z","timestamp":1777791149506,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Biol Rhythms"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Casein kinase 1\u03b5 (CK1\u03b5) performs key phosphorylation reactions in the circadian clock mechanism that determine period. We show that the central clock protein PERIOD2 (PER2) not only acts as a transcriptional repressor but also inhibits the autoinactivation of CK1\u03b5, thereby promoting CK1\u03b5 activity. Moreover, PER2 reciprocally regulates CK1\u03b5\u2019s ability to phosphorylate other substrates. On output pathway substrates (e.g., P53), PER2 inhibits the activity of CK1\u03b5. However, in the case of central clock proteins (e.g., CRYPTOCHROME2), PER2 stimulates the CK1\u03b5-mediated phosphorylation of CRY2. CK1\u03b5 activity is temperature compensated on the core clock substrate CRY2 but not on output substrates, for example, the physiological output protein substrate P53 and its nonphysiological correlate, bovine serum albumin (BSA). These results indicate heretofore unrecognized pivotal roles of PER2; it not only regulates the central transcription\/translation feedback loop but also differentially controls kinase activity CK1\u03b5 in its phosphorylation of central clock (e.g., CRY2) versus output (e.g., P53) substrates.<\/jats:p>","DOI":"10.1177\/0748730415582127","type":"journal-article","created":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T00:30:39Z","timestamp":1432081839000},"page":"206-216","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["PER2 Differentially Regulates Clock Phosphorylation versus Transcription by Reciprocal Switching of CK1\u03b5 Activity"],"prefix":"10.1177","volume":"30","author":[{"given":"Ximing","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Vanderbilt University, Nashville, 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