| Project/Area Number |
25461428
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | University of the Ryukyus |
|---|
Principal Investigator |
MORI Naoki 琉球大学, 医学(系)研究科(研究院), 教授 (10220013)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | HTLV-1 / 成人T細胞白血病 / NF-κB / IκB-ζ / Tax / LMP-1 / CD30 / EBウイルス / インターフェロン応答遺伝子 |
|---|
| Outline of Final Research Achievements |
NF-κB activation is important in the transformation and development process in ATL, Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL). HTLV-1 Tax, EB virus (EBV) LMP-1 and ligand-independent signaling by over- expressed CD30 are known to cause permanent activation of NF-κB in lymphomas. However, hyper-activation of NF-κB triggers cellular senescence and apoptosis. IκB-ζ, an inducible regulator of NF-κB, was constitutively expressed in the nuclei of ATL, BL and HL cells. Expression of Tax, LMP-1 and CD30 trans-activated the IκB-ζ gene through NIK/IKK/NF-κB pathway. IκB-ζ induced the expression of NF-κB- and IFN-regulatory genes in T cells. IκB-ζ enhanced Tax-induced transactivation of Bcl-3 and iNOS. Interestingly, IκB-ζ inhibited NF-κB activation by Tax, LMP-1 and CD30, and HTLV-1 transcription. NF-κB-induced IκB-ζ modulates NF-κB activation, resulting in a fine balance that ultimately endows a net evolutionary benefit to the survival of lymphoma cells.
|
