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An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals
http://hdl.handle.net/2237/00033501
http://hdl.handle.net/2237/000335017314d485-d1e4-459c-88a9-ea7ca8705998
名前 / ファイル | ライセンス | アクション |
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CellChemBiol-rev2-Hirota (4.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-02-09 | |||||
タイトル | ||||||
タイトル | An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals | |||||
言語 | en | |||||
著者 |
Miller, Simon
× Miller, Simon× Aikawa, Yoshiki× Sugiyama, Akiko× Nagai, Yoshiko× Hara, Aya× Oshima, Tsuyoshi× Amaike, Kazuma× Kay, Steve A.× Itami, Kenichiro× Hirota, Tsuyoshi |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | circadian clock | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | cryptochrome | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | small-molecule modulator | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | chemical biology | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | X-ray crystallography | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian circadian clock that selectively controls CRY1. Cell-based circadian chemical screening identified a thienopyrimidine derivative KL201 that lengthened the period of circadian rhythms in cells and tissues. Functional assays revealed stabilization of CRY1 but not CRY2 by KL201. A structure-activity relationship study of KL201 derivatives in combination with X-ray crystallography of the CRY1-KL201 complex uncovered critical sites and interactions required for CRY1 regulation. KL201 bound to CRY1 in overlap with FBXL3, a subunit of ubiquitin ligase complex, and the effect of KL201 was blunted by knockdown of FBXL3. KL201 will facilitate isoform-selective regulation of CRY1 to accelerate chronobiology research and therapeutics against clock-related diseases. | |||||
言語 | en | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | ファイル公開:2021-09-17 | |||||
言語 | ja | |||||
出版者 | ||||||
出版者 | Elsevier | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.chembiol.2020.05.008 | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 2451-9456 | |||||
書誌情報 |
en : Cell Chemical Biology 巻 27, 号 9, p. 1192-1198.e5, 発行日 2020-09-17 |
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著者版フラグ | ||||||
値 | author |