Mechanistic insight into CCR4-NOT deadenylase-mediated heart function control and its potential application for therapeutics
| Project/Area Number |
26293050
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Akita University |
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Principal Investigator |
Kuba Keiji 秋田大学, 医学(系)研究科(研究院), 教授 (10451915)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | CCR4-NOT / heart failure / deadenylase / CNOT3 / 心不全 / デアデニレース / オートファジー / ネクローシス / RNA代謝 / 脱アデニル化 / 循環器 / RNA創薬 / 遺伝子改変マウス / ＣＣＲ４－ＮＯＴ / poly(A) / 心臓 |
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| Outline of Final Research Achievements |
In this study, we analyzed the mechanisms how CCR4-NOT deadenylase regulates mRNA decay and nucleotide metabolism in controlling heart functions. mRNA decay by CCR4-NOT complex was revealed to alter adenine nucleotide levels in the heart. In addition, bulk mRNA poly(A) shortening and alteration of nucleotide levels were sensed by an autophagy molecule, which is crucial for cardiomyocyte survival. Furthermore, CCR4-NOT-mediated adenine nucleotide regulation was also shown to affect energy-sensing signaling pathway. Both pathways are likely important for CCR4-NOT-mediated heart function control. Finally, we conducted chemical compound screening for CCR4-NOT deadenylase inhibitors.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage2017
Author(s)
Sato T, Sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, Yamaguchi T, Kimura A, Fukamizu A, Penninger JM, Reversade B, Ito H, Imai Y, Kuba K
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Journal Title
Cardiovasc Res.
Volume: 113(7)
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy.2017
Author(s)
Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
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Journal Title
JCI insight
Volume: 2
Pages: 89462-89478
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The arachidonic acid metabolome as conserved regulator of cholesterol metabolism.2014
Author(s)
Demetz E, Schroll A, Auer K, Heim C, Patsch JR, Eller P, Theurl M, Lener D, Stanzl U, Seifert M, Haschka D, Asshoff M, Dichtl S, Nairz M, Huber E, Stadlinger M, Li X, Pallweber P, Scharnagl H, Stojakovic T, Marz W, Kleber ME, Garlaschelli K, Uboldi P, Catapano AL, Kuba K, Imai Y, Arita M, Tancevski I.
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Journal Title
Cell Metab
Volume: 20
Pages: 787-798
DOI
Related Report
Peer Reviewed / Open Access
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