| 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)
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| 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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