Analysis of the novel function of SCF-Fbw7
Project/Area Number |
24570151
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | Fbw7 / GATA3 / T 細胞分化 / タンパク分解 / 蛋白分解 / T cell |
Outline of Final Research Achievements |
We demonstrated that Fbw7 bound to, ubiquitylated, and destabilized GATA3 using overexpressed proteins in cultured cells. Cdc4 phosphodegron (CPD) candidate sequences, consensus Fbw7 recognition domains, was identified in GATA3. Fbw7-mediated ubiquitylation and degradation required for phosphorylation of Thr-156 in CPD, and CDK2 was identified as a responsive kinase. Conditional inactivation of Fbw7 in mice T-cell development resulted in reduced thymic and splenic subcell proportions, and augmented GATA3 in some lineages. Fbw7 deficiency skewed CD8 SP lineage differentiation, which exhibited a higher incidence of apoptosis. Similar perturbations during development of CD8 positive cells were reported with transgenic mice, which enforced GATA3 expression during T-cell development. These observations suggest Fbw7-mediated GATA3 regulation with CDK2-mediated phosphorylation of CPD contributes to the precise differentiation of T-cell lineages.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Fbw7 targets GATA3 through cyclin-dependent kinase 2-dependent proteolysis and contributes to regulation of T-cell development2014
Author(s)
Kitagawa, K., Shibata, K., Matsumoto, A., Matsumoto, M., Ohhata, T., Nakayama, K. I., Niida, H., Kitagawa, M.
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Journal Title
Mol. Cell. Biol.
Volume: 34
Issue: 14
Pages: 2732-2744
DOI
Related Report
Peer Reviewed / Open Access
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