Role of IRF-4 in adult T cell Leukemia/lymphoma

IRF-4 在成人 T 细胞白血病/淋巴瘤中的作用

• 批准号: 15390117
• 负责人: MATSUYAMA Toshifumi
• 金额: $ 4.67万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390117/
• 关键词: interferon; IRF-4; ATL; ISRE; dendritic cell; EBI-1

1.Optimal binding motif of IRF-4 is identified, by selection and amplification binding(SAAB) method. IRF-4 prefers to the motif, 5'-GAAA-3' flanked by CpG. Similar motifs are found in the promoter of human TRAIL and DCIR.2.By analyzing IRF-4 deficient dendritic cells, we show that IRF-4 is important for CD11b^<high>CD8α conventional DCs. IRF-4 and IRF-8 were expressed in the majority of CD11b^<high>CD4^+CD8α^-DCs and CD CD11b^<low>CD8α^+ DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.3.We investigated the transcriptional control of IRF-4 in B lymphocytes. The IRF-4 promoter analysis reveals that the region between -51 and -28 was required for the basal promoter activity. UV photocrosslinking assays identified a novel 60 kDa protein with a similar sequence preference.4.To clarify the direct involvement of IRF-4 in ATL proliferation, we have applied IRF-4 specific siRNA, however, at present, every attempt to reduce the expression of IRF-4 was found unsuccessful.5.By applying membrane array, we found EBI-1/CCR7 may be one of the target genes of IRF-4. It is consistent with our previous finding that ATLL cells express EBI-1/CCR7 and IRF-4 concomitantly.

1.通过选择和扩增结合(SAAB)方法确定了IRF-4的最佳结合基序。IRF-4更喜欢CpG侧翼的5‘-GAAA-3’基序。2.通过对缺乏Irf-4的树突状细胞的分析，我们发现Irf-4在CD11b和CD8高表达的α常规树突状细胞中起重要作用。IRF-4和IRF-8在大多数CD11b1+CD8α+DC和CD11b1+CD8α+DC中分别以相互排斥的方式表达。这些结果表明，IRF-4和IRF-8选择性地在表达它们的DC亚群的发育过程中发挥关键作用。3.我们研究了IRF-4在B淋巴细胞中的转录调控。IRF-4启动子分析表明，-51和-28之间的区域是基本启动子活性所必需的。4.为了阐明IRF-4在ATL增殖中的直接作用，我们应用了IRF-4特异的siRNA，但目前所有试图降低IRF-4表达的尝试都没有成功。5.应用膜阵列，我们发现EBI-1/CCR7可能是IRF-4的靶基因之一。这与我们以前的发现一致，ATLL细胞同时表达EBI-1/CCR7和IRF-4。

项目成果

Paramagnetic NMR study of Cu(2+)-IDA complex localization on a protein surface and its application to elucidate long distance information.

Cu(2 )-IDA 复合物在蛋白质表面定位的顺磁 NMR 研究及其在阐明长距离信息中的应用。

• 发表时间: 2004
• 期刊: FEBS Lett.2004 566:157-61.. 第566巻
• 作者: Horinouchi I.;Nakazato H.;Kawano T.;Iyama K.;Furuse A.;Arizono K.;Machida J.;Sakamoto T.;Endo F.;Hattori S.;Nomura M
• 通讯作者: Nomura M

Disruption of tumor necrosis factor recepter p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts

肿瘤坏死因子受体 p55 的破坏会损害实验诱导的硬皮病皮肤成纤维细胞中的胶原蛋白周转

• 发表时间: 2003
• 期刊: Arthritis & Rheumatism 第48巻第4号
• 作者: Mizoshita;T.;Inada;K.;Tsukamoto;T.;Nozaki;K.;Job;T.;Itoh;M.;Yamamura;Y.;Ushijima;T.;Nakamura;S.;Tatematsu.M.;Hiroyuki Murota
• 通讯作者: Hiroyuki Murota

Critical roles of interferon regulatory factor- 4(IRF-4) in CD11bhighCD8alpha-dendritic cell development.

干扰素调节因子 4 (IRF-4) 在 CD11bhighCD8α 树突状细胞发育中的关键作用。

• 发表时间: 2004
• 期刊: Proc Natl Acad Sci USA. 第101巻
• 作者: Nomura M;Suzuki S et al.;Nishiya N et al.;Yamamoto Y et al.;Nomura M et al.;Suzuki S
• 通讯作者: Suzuki S

Critical roles of interferon regulatery factor-4(IRF-4) in CD11bhighCD8alpha-dendritic cell development.

干扰素调节因子 4 (IRF-4) 在 CD11bhighCD8α 树突状细胞发育中的关键作用。

• 发表时间: 2004
• 期刊: Proc Natl Acad Sci USA. 第101巻
• 作者: Okumura K.;Nakamura K.;Hisatomi Y.;Nagano K.;Tanaka Y.;Terada K.;Sugiyama T.;Umeyama K.;Matsumoto K.;Yamamoto T.;Endo F.;Mabuchi T et al.;Suzuki S
• 通讯作者: Suzuki S

Identification of a novel GC-rich binding protein that binds to an indispensable element for constitutive IRF-4 promoter activity in B cells.

鉴定出一种新型富含 GC 的结合蛋白，该蛋白与 B 细胞中 IRF-4 启动子组成型活性不可缺少的元件结合。

• 发表时间: 2004
• 期刊: Mol Immunol 第41巻
• 作者: Tanaka;S. et al.;Nishiya N
• 通讯作者: Nishiya N