| Project/Area Number |
21591225
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Keiko 愛知医科大学, 医学部, 准教授 (10139652)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | マルトリンパ腫 / アポトーシス / プロテオミクス / NF-κB / マイクロアレイ法 / NF-kB |
|---|
| Research Abstract |
Four recurrent chromosomal translocations, t(11 ; 18)(q21 ; q21), t(1 ; 14)(p22 ; q32), t(14 ; 18)(q32 ; q21), and t(3 ; 14)(p14.1 ; q32) have been implicated in the pathogenesis of mucosa associated lymphoid tissue(MALT) lymphoma. We have identified an API2-MALT1 chimeric oncoprotein in the t(11 ; 18)(q21 ; q21) translocation. The API2-MALT1 can bypass this usual BCL10/MALT1 cellular signaling pathway linked to NF-κB activation, thereby inducing antigen receptor-independent proliferation of lymphocytes. Moreover, API2-MALT1-induced NF-κB activation may contribute to anti-apoptotic effect through NF-κB-mediated upregulation of apoptotic inhibitor genes. In fact, we recently demonstrated that API2-MALT1 can induce transactivation of the API2 gene through NF-κB activation, thus highlighting a novel positive feedback-loop mechanism of self-activation by up-regulating its own expression in t(11 ; 18) MALT lymphomas. We also demonstrated that API2-MALT1 possesses anti-apoptotic effect, in part, through its direct interaction with apoptotic regulators. We therefore hypothesize that anti-apoptotic effect by API2-MALT1 may be mediated by in one way its interaction with apoptotic regulators as well as by in another way its self-activation resulting in unremitting NF-κB activation. Finally, further studies can be expected to stimulate research into the development of therapeutic drugs
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