The SCF ubiquitin ligase regulates calcineurin signaling through degradation of RCAN1, an inhibitor of calcineurin.
| Project/Area Number |
20570010
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genetics/Genome dynamics
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
KISHI Tsutomu The Institute of Physical and Chemical Research, 大学院・生命理工学研究科, グローバルCOE研究員 (80260024)
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| Project Period (FY) |
2008 – 2011
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | シグナル伝達 / 蛋白質分解 / カルシウム / ユビキチン / SCF / カルシニューリン / カルシウム・シグナリング / フィードバック・インヒビター / ユビキチンリガーゼ / 細胞周期 / フィードバックインヒビター |
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| Research Abstract |
The highly conserved RCAN family of proteins regulates the serine/threonine protein phosphatase calcineurin, which is required for the expression of genes involved in Ca^<2+->dependent processes such as the control of memory, apoptosis, T cell activation, cell cycle and cardiac muscle growth and differentiation. However, RCANs regulate calcineurin through two paradoxical actions: they act as feedback inhibitors of calcineurin, whereas their phosphorylation stimulates calcineurin. Here we showed that phosphorylation of RCAN triggers degradation through the SCF ubiquitin ligase complex in yeast and in human. Degradation of phosphorylated RCAN is required to mitigate inhibition of calcineurin by RCAN and results in activation of calcineurin in response to changes in Ca^<2+> concentration. Such phosphorylayion was counteracted by dephosphorylation of RCAN, which was promoted by Ca^<2+->stimulated calcineurin. These results provide insight into the mechanism involved in maintaining proper responses to Ca^<2+> signals.
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Report
(4 results)
Research Products
(12 results)
