Molecular mechanism of the selective AID targeting at the IgV-region

针对 IgV 区域的选择性 AID 的分子机制

• 批准号: 23390122
• 负责人: SAKAGUCHI NOBUO
• 金额: $ 12.65万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390122/
• 关键词: 免疫学; ゲノム; 遺伝子

To elucidate the molecular mechanism of GANP interacted with AID in generation of antibody affinity maturation in B cells, GANP interacting proteins was identified in the nuclear extract from human B cell line Ramos cells. GANP interacts with histones and induces chromatin modification with the acetylation though the GANP HAT domain. GANP binds to the rearranged IgV region. This position is relaxed during IgV transcription. Transcription complex similarly retains during the IgV transcription, which presumably maintains the DNA configuration for continuation and providing the opportunity of AID accession. GANP recruits AID towards the selective site of the rearranged IgV region to augment mutation frequency. We further clarified the role of GANP in the choice of DNA repair pathways after the DNA injury caused by AID at the IgV region gene. GANP is essentially involved in maintenance of DNA and the genome integrity for efficient DNA mutations during antibody affinity maturation.

为了阐明GANP与AID相互作用在B细胞中产生抗体亲和力成熟的分子机制，在来自人B细胞系拉莫斯细胞的核提取物中鉴定GANP相互作用蛋白。GANP与组蛋白相互作用并通过GANP HAT结构域诱导具有乙酰化的染色质修饰。GANP与重排的IgV区域结合。该位置在IgV转录期间是松弛的。转录复合物在IgV转录期间类似地保留，这可能维持DNA构型以供延续并提供AID加入的机会。GANP将AID募集到重排的IgV区域的选择性位点，以增加突变频率。我们进一步阐明了GANP在AID在IgV区基因引起DNA损伤后DNA修复途径选择中的作用。GANP基本上涉及DNA和基因组完整性的维持，以在抗体亲和力成熟期间进行有效的DNA突变。

项目成果

Role of mammalian TREX-2 component GANP in HIV-1 infection

哺乳动物 TREX-2 成分 GANP 在 HIV-1 感染中的作用

• 发表时间: 2013
• 作者: Maeda K;Almofty SA;Singh SK;Eid MMA;Shimoda M;Ikeda T;Shida H;Koito A;Pham P;Goodman MF;and Sakaguchi N.
• 通讯作者: and Sakaguchi N.

Molecular Mechanism of Immunoglobulin V-Region Diversification Regulated by Transcription and RNA Metabolism in Antigen-Driven B Cells

抗原驱动B细胞转录和RNA代谢调节免疫球蛋白V区多样化的分子机制

• DOI: 10.1111/j.1365-3083.2011.02557.x
• 发表时间: 2011
• 期刊: Scandinavian Journal of Immunology
• 影响因子: 3.7
• 作者: Sakaguchi N;et al
• 通讯作者: et al

Targeting the rearranged immunoglobulin V-region locus in B-cells by the histone acetyl transcriptase activity of GANP

通过 GANP 的组蛋白乙酰转录酶活性靶向 B 细胞中重排的免疫球蛋白 V 区基因座

• 发表时间: 2012
• 作者: Ishii K.;Li TC.;Yoshizaki S.;Shiota T.;Kato T.;Takeda N.;Wakita T.;Kazuhiko Maeda
• 通讯作者: Kazuhiko Maeda

乳腺上皮細胞におけるエストロゲンが誘導するDNA損傷においてGANPは重要な役割を果たす

GANPs 在雌激素诱导的乳腺上皮细胞 DNA 损伤中发挥重要作用

• 发表时间: 2012
• 作者: 古賀友紹;佐々木文之;佐伯和子;奥野利明;横溝岳彦;阪口薫雄
• 通讯作者: 阪口薫雄

Mammalian Leng8 carrying a Sac3/GANP homologous region unregulated in germinal center B cells is involved in regulation of BCR-mediated proliferation

携带 Sac3/GANP 同源区的哺乳动物 Leng8 在生发中心 B 细胞中不受调节，参与 BCR 介导的增殖的调节

• 发表时间: 2013
• 作者: Kuwahara;K.;Kitabatake;M.;Kitamura;D.;Sakaguchi;N.
• 通讯作者: N.