Molecular analysis of anti-apoptotic action in MALT lymphoma and its clinical application for diagnosis and treatment.

MALT淋巴瘤抗凋亡作用的分子分析及其临床诊断和治疗应用。

• 批准号: 17591023
• 负责人: HOSOKAWA Yoshitaka
• 金额: $ 2.24万
• 依托单位: Aichi Medical University School of Medicine (2006)Aichi Cancer Center Research Institute (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591023/
• 关键词: Malignant lymphoma; apoptosis; Chromosome translocation; プロテオミクス

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.

API 2-MALT 1。t（11; 18）（q21; q21）是粘膜相关淋巴组织（MALT）型淋巴瘤中的特征性染色体易位，并且该易位导致API 2（凋亡抑制剂2，也称为c-IAP 2）-MALT 1（粘膜相关淋巴瘤易位基因1）的嵌合转录物。为了鉴定结合API 2-MALT 1嵌合蛋白的蛋白，我们采用免疫共沉淀和SDS PAGE分析，然后通过液相色谱-电喷雾串联质谱。结果表明，Smac、Htra 2和TRAF 2为API 2-MALT 1结合蛋白，免疫沉淀分析表明，异位表达的API 2-MALT 1蛋白确实与这些内源性蛋白结合。此外，API 2-MALT 1蛋白显着抑制Smac促进的细胞凋亡在紫外线照射的HeLa细胞。这些数据有力地表明，API 2-MALT 1可以阻断凋亡，至少部分，通过抑制Smac介导的凋亡途径。API 2-MALT 1的分子机制及其临床应用有待进一步研究。

项目成果

Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying the antiapoptotic of API2-MALT1 fusion protein

MALT淋巴瘤的分子发病机制：API2-MALT1融合蛋白抗凋亡的两条信号通路

• 发表时间: 2006
• 期刊: Leukemia 20
• 作者: Hamaguchi I;Morisada T;Azuma M;Murakami K;Kuramitsu M;Mizukami T;Ohbo K;Yamaguchi K;Oike Y;Dumont DJ;Suda T;Nakagawa M et al.
• 通讯作者: Nakagawa M et al.

Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying anti-apoptotic effect of API2-MALT1 fusion protein

MALT淋巴瘤的分子发病机制：API2-MALT1融合蛋白抗凋亡作用的两条信号通路

• 期刊: Leukemia (In press)
• 作者: Tsujimura K;et al.;Nakagawa et al.
• 通讯作者: Nakagawa et al.

Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.

API2-MALT1 融合蛋白参与 t(11;18)(q21;q21) MALT 淋巴瘤的抗凋亡作用。

• 发表时间: 2005
• 期刊: Apoptosis 10
• 作者: Hosokawa Y et al.

API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-кB binding elements; evidence for a positive feed-back loop pathway resulting in unremitting NF-кB activation.

API2-MALT1 融合蛋白通过 NF-кB 结合元件诱导 API2 基因的转录激活；证据表明正反馈环路途径导致 NF-кB 持续激活。

• 发表时间: 2005
• 期刊: Biochem.Biophys.Res.Commun. 334
• 作者: Hosokawa Y;Suzuki H;Nakagawa M;Lee TH;Seto M.
• 通讯作者: Seto M.

API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements; evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation.

API2-MALT1 融合蛋白通过 NF-κB 结合元件诱导 API2 基因的转录激活；证据表明正反馈环路途径导致 NF-κB 持续激活。

• 发表时间: 2005
• 期刊: Biochem. Biophys. Res. Commun 334
• 作者: Nagamatsu G;Ohmura M;Mizukami T;Hamaguchi I;Hirabayashi S;Yoshida S;Hata Y;Suda T;Ohbo K;Hosokawa Y et al.
• 通讯作者: Hosokawa Y et al.