Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Jang, J. | - |
dc.contributor.author | Chung, S. | - |
dc.contributor.author | Choi, Y. | - |
dc.contributor.author | Lim, H.Y. | - |
dc.contributor.author | Son, Y. | - |
dc.contributor.author | Chun, Sung Kook | - |
dc.contributor.author | Son, G.H. | - |
dc.contributor.author | Kim, Kyungjin | - |
dc.contributor.author | Suh, Y.-G. | - |
dc.contributor.author | Jung, J.-W. | - |
dc.date.available | 2018-04-11T03:46:20Z | - |
dc.date.created | 2018-03-30 | - |
dc.date.issued | 2018-05 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/6147 | - |
dc.description.abstract | Aims: We have previously identified a chemical scaffold possessing 2-ethoxypropanoic acid (designated as KS15) that directly binds to the C-terminal region of cryptochromes (CRYs: CRY1 and CRY2) and enhances E-box-mediated transcription. However, it is still unclear how KS15 impairs the feedback actions of the CRYs and which chemical moieties are functionally important for its actions. Main methods: The E-box-mediated transcriptional activities were mainly used to examine the effects of KS15 and its derivatives. Co-immunoprecipitation assays accompanied by immunoblotting were employed to monitor protein-protein associations. We also examined the effects of KS15 and selected derivatives on circadian molecular rhythms in cultured cells. Key findings: The present study shows that KS15 inhibits the interaction between CRYs and Brain-Muscle-Arnt-Like protein 1 (BMAL1), thereby impairing the feedback actions of CRYs on E-box-dependent transcription by CLOCK:BMAL1 heterodimer, an indispensable transcriptional regulator of the mammalian circadian clock. Subsequent structure-activity relationship analyses using a well-designed panel of derivatives identified the structural requirements for the effects of KS15 on CRY-evoked regulation of E-box-mediated transcription. We found that KS15 and several derivatives significantly reduce the amplitude and delayed the phase of molecular circadian rhythms in fibroblast cultures. Significance: Taken together, our results provide valuable information on the molecular mode-of-action as well as the chemical components of the CRYs inhibitor that pharmacologically impact on the transcriptional activity of the CLOCK:BMAL1 heterodimer. © 2018 Elsevier Inc. | - |
dc.language | English | - |
dc.publisher | Elsevier BV | - |
dc.title | The cryptochrome inhibitor KS15 enhances E-box-mediated transcription by disrupting the feedback action of a circadian transcription-repressor complex | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.lfs.2018.03.022 | - |
dc.identifier.scopusid | 2-s2.0-85043994328 | - |
dc.identifier.bibliographicCitation | Life Sciences, v.200, pp.49 - 55 | - |
dc.description.isOpenAccess | FALSE | - |
dc.subject.keywordAuthor | Circadian rhythm | - |
dc.subject.keywordAuthor | Circadian clock | - |
dc.subject.keywordAuthor | Cryptochromes (CRYs) | - |
dc.subject.keywordAuthor | CLOCK:BMAL1 heterodimer | - |
dc.subject.keywordAuthor | KS15 | - |
dc.subject.keywordAuthor | 2-Ethoxypropanoic acid | - |
dc.subject.keywordPlus | MAMMALIAN CRY1 | - |
dc.subject.keywordPlus | C-TERMINUS | - |
dc.subject.keywordPlus | CLOCK | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | TARGETS | - |
dc.subject.keywordPlus | - | |
dc.subject.keywordPlus | MCRY2 | - |
dc.citation.endPage | 55 | - |
dc.citation.startPage | 49 | - |
dc.citation.title | Life Sciences | - |
dc.citation.volume | 200 | - |
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