2005 Fiscal Year Final Research Report Summary
HTLV-I Tax dysregulates β-catenin signaling
| Project/Area Number |
16590951
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | University of the Ryukyus |
|---|
Principal Investigator |
MORI Naoki University of the Ryukyus, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (10220013)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | HTLV-1 / ATL / Tax / β-catenin / CREB / Akt / P13K / GSK-3β |
|---|
| Research Abstract |
Dysregulation of β-catenin signaling has been implicated in the malignant transformation of cells. However, the role of β-catenin in human T-cell leukemia virus type 1 (HTLV-1)-induced transformation of T cells is unknown. Here we found that β-catenin protein was overexpressed in the nucleus and that β-catenin-dependent transcription was significantly enhanced in Tax-positive HTLV-1-infected T-cell lines, compared to Tax-negative HTLV-1-infected T-cell-lines. Transient transfection of Tax appeared to enhance the β-catenin-dependent transcription by stabilizing the β-catenin protein, via activation of the cAMP response element-binding protein. The HTLV-1-infected T-cell lines overexpressing β-catenin also showed increased Akt activity, via Tax activation of cAMP response element-binding protein, resulting in the phosphorylation and inactivation of glycogen synthase kinase-3β, which phosphorylates β-catenin for ubiquitination. The phosphatidylinositol 3-kinase inhibitor, LY294002 reduced β-catenin expression in Tax-positive T-cell lines, and inactivation of glycogen synthase kinase-3β by lithium chloride restored β-catenin expression in Tox-negative T-cell lines. Finally, we showed that dominant-negative Akt inhibited the Tax-induced β-catenin-dependent transcription. These results indicated that Tax activates β-catenin through the Akt signaling pathway. Our findings suggest that activation of β-catenin by Tax may be important in the transformation of T cells by HTLV-1 infection.
|
Research Products
(50 results)
