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  1. I300 トランスフォーマティブ生命分子研究所
  2. I300a 雑誌掲載論文
  3. 学術雑誌

An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals

http://hdl.handle.net/2237/00033501
http://hdl.handle.net/2237/00033501
7314d485-d1e4-459c-88a9-ea7ca8705998
名前 / ファイル ライセンス アクション
CellChemBiol-rev2-Hirota.pdf CellChemBiol-rev2-Hirota (4.8 MB)
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

WEKO 103360

en Miller, Simon

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Aikawa, Yoshiki

× Aikawa, Yoshiki

WEKO 103361

en Aikawa, Yoshiki

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Sugiyama, Akiko

× Sugiyama, Akiko

WEKO 103362

en Sugiyama, Akiko

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Nagai, Yoshiko

× Nagai, Yoshiko

WEKO 103363

en Nagai, Yoshiko

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Hara, Aya

× Hara, Aya

WEKO 103364

en Hara, Aya

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Oshima, Tsuyoshi

× Oshima, Tsuyoshi

WEKO 103365

en Oshima, Tsuyoshi

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Amaike, Kazuma

× Amaike, Kazuma

WEKO 103366

en Amaike, Kazuma

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Kay, Steve A.

× Kay, Steve A.

WEKO 103367

en Kay, Steve A.

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Itami, Kenichiro

× Itami, Kenichiro

WEKO 103368

en Itami, Kenichiro

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Hirota, Tsuyoshi

× Hirota, Tsuyoshi

WEKO 103369

en 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 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
内容記述タイプ Abstract
内容記述
内容記述 ファイル公開:2021-09-17
言語 ja
内容記述タイプ Other
出版者
言語 en
出版者 Elsevier
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
著者版フラグ
値 author
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