Isoform selectivity of circadian clock proteins CRY1 and CRY2 analyzed by new chemical tools
Project/Area Number |
18H02402
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 43030:Functional biochemistry-related
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Research Institution | Nagoya University |
Principal Investigator |
Hirota Tsuyoshi 名古屋大学, トランスフォーマティブ生命分子研究所, 特任准教授 (50372412)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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Keywords | 概日時計 / ケミカルバイオロジー / 化合物 / CRYタンパク質 / 選択性 |
Outline of Final Research Achievements |
CRY proteins constituting the mammalian circadian clock have two closely related homologs, CRY1 and CRY2. Functional differences of these proteins provide a model system to tackle fundamental questions regarding how the circadian clock precisely oscillates and controls physiological outputs. In this study, we discovered isoform-selective compounds against CRY1 and CRY2, and by analyzing their mechanism of action, revealed molecular mechanism underlying difference of CRY1 and CRY2.
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Academic Significance and Societal Importance of the Research Achievements |
CRY1とCRY2は配列が非常によく似ているため、選択的な化合物のデザインは困難であった。本研究では、配列がほぼ同一である化合物結合ポケットに対して選択性を生み出すユニークな化合物を見出し、それらの作用機構を解明した。概日時計が乱れるリズム障害は現代社会における深刻な問題となっており、本研究による制御機構の理解と特異的な調節ツールの開発は、CRYを利用した疾患治療法の開発に向けた重要な足がかりとなるであろう。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Isoform-selective regulation of mammalian cryptochromes2020
Author(s)
Miller Simon、Son You Lee、Aikawa Yoshiki、Makino Eri、Nagai Yoshiko、Srivastava Ashutosh、Oshima Tsuyoshi、Sugiyama Akiko、Hara Aya、Abe Kazuhiro、Hirata Kunio、Oishi Shinya、Hagihara Shinya、Sato Ayato、Tama Florence、Itami Kenichiro、Kay Steve A.、Hatori Megumi、Hirota Tsuyoshi
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Journal Title
Nature Chemical Biology
Volume: -
Issue: 6
Pages: 676-685
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth.2019
Author(s)
Oshima T, Niwa Y, Kuwata K, Srivastava A, Hyoda T, Tsuchiya Y, Kumagai M, Tsuyuguchi M, Tamaru T, Sugiyama A, Ono N, Zolboot N, Aikawa Y, Oishi S, Nonami A, Arai F, Hagihara S, Yamaguchi J, Tama F, Kunisaki Y, Yagita K, Ikeda M, Kinoshita T, Kay SA, Itami K, Hirota T.
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Journal Title
Science Advance
Volume: 23
Issue: 1
Pages: 9060-9060
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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