2006 Fiscal Year Final Research Report Summary
Molecular analysis of anti-apoptotic action in MALT lymphoma and its clinical application for diagnosis and treatment.
| Project/Area Number |
17591023
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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 School of Medicine (2006)
Aichi Cancer Center Research Institute (2005) |
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Principal Investigator |
HOSOKAWA Yoshitaka Aichi Medical University School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (60229193)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Malignant lymphoma / apoptosis / Chromosome translocation |
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| Research Abstract |
API2-MALT1. t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in chimeric transcript of API2 (Apoptosis Inhibitor 2, also known as c-IAP2)-MALT1 (Mucosa-Associated Lymphoma Translocation gene 1). To identify proteins that bind API2-MALT1 chimeric protein, we employed coimmunoprecipitation and SDS PAGE analysis, followed by liquid chromatography-electrospray ionization tandem mass spectrometry. As a result, Smac, Htra2, and TRAF2 were identified as API2-MALT1-binding proteins.
Immunoprecipitation analysis demonstrated that ectopically expressed API2-MALT1 protein indeed binds to these endogeneous proteins. Furthermore, API2-MALT1 protein significantly inhibited Smac-promoted apoptosis in UV irradiated HeLa cells. These data strongly suggest that API2-MALT1 can block apoptosis, at least in part, by inhibiting Smac-mediated apoptotic pathway. Further study is warranted to investigate the detailed molecular mechanism of API2-MALT1 and its clinical application.
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