IkappaB-zeta, a regulator of NF-kappaB, contributes to the pathogenesis of ATL
| Project/Area Number |
25461428
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
MORI Naoki 琉球大学, 医学(系)研究科(研究院), 教授 (10220013)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(33 results)
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[Presentation] Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia-lymphoma cells2014
Author(s)
Hiroaki Taniguchi, Hiroo Hasegawa, Daisuke Sasaki, Koji Ando, Yasushi Sawayama, Daisuke Imanishi, Jun Taguchi, Yoshitaka Imaizumi, Tomoko Hata, Kunihiro Tsukasaki, Yanagihara Katsunori, Naoki Mori, Yasushi Miyazaki
Organizer
19th Congress of the European Hematology Association
Place of Presentation
Milan（Italy）
Year and Date
2014-06-12 – 2014-06-15
Related Report
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[Presentation] 成人T細胞白血病リンパ腫に対するHSP90阻害薬NVP-AUY922の抗腫瘍効果2013
Author(s)
谷口広明, 長谷川寛雄, 佐々木大介, 安東恒史, 澤山靖, 今西大介, 今泉芳孝, 田口潤, 波多智子, 塚崎邦弘, 森直樹, 柳原克紀, 宮崎泰司
Organizer
第6回HTLV-1研究会・シンポジウム
Place of Presentation
東京大学医科学研究所講堂（東京都港区）
Related Report
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