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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 |
|---|---|---|
CellChemBiol-rev2-Hirota (4.8 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 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resource | http://purl.org/coar/resource_type/c_6501 | |||||
| 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 | |||||
