The cryptochrome inhibitor KS15 enhances E-box-mediated transcription by disrupting the feedback action of a circadian transcription-repressor complex
DC Field | Value | Language |
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dc.contributor.author | Jang, Jaebong | - |
dc.contributor.author | Chung, Sooyoung | - |
dc.contributor.author | Choi, Youjeong | - |
dc.contributor.author | Lim, Hye Young | - |
dc.contributor.author | Son, Yeongeon | - |
dc.contributor.author | Chun, Sung Kook | - |
dc.contributor.author | Son, Gi Hoon | - |
dc.contributor.author | Kim, Kyungjin | - |
dc.contributor.author | Suh, Young-Ger | - |
dc.contributor.author | Jung, Jong-Wha | - |
dc.date.accessioned | 2021-09-02T11:40:46Z | - |
dc.date.available | 2021-09-02T11:40:46Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2018-05-01 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/75583 | - |
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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.subject | MAMMALIAN CRY1 | - |
dc.subject | C-TERMINUS | - |
dc.subject | CLOCK | - |
dc.subject | CANCER | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | IDENTIFICATION | - |
dc.subject | TARGETS | - |
dc.subject | - | |
dc.subject | MCRY2 | - |
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.contributor.affiliatedAuthor | Son, Gi Hoon | - |
dc.identifier.doi | 10.1016/j.lfs.2018.03.022 | - |
dc.identifier.scopusid | 2-s2.0-85043994328 | - |
dc.identifier.wosid | 000429665600007 | - |
dc.identifier.bibliographicCitation | LIFE SCIENCES, v.200, pp.49 - 55 | - |
dc.relation.isPartOf | LIFE SCIENCES | - |
dc.citation.title | LIFE SCIENCES | - |
dc.citation.volume | 200 | - |
dc.citation.startPage | 49 | - |
dc.citation.endPage | 55 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
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.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 | - |
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