2014 Fiscal Year Final Research Report
Analysis of the novel function of SCF-Fbw7
| Project/Area Number |
24570151
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | Fbw7 / GATA3 / T 細胞分化 |
|---|
| 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.
|
| Free Research Field |
分子生物学
|
