Role of GANP-mediated hypermutation

• Project/Area Number: 22590436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kumamoto University
• Principal Investigator: MAEDA Kazuhiko 熊本大学, 大学院・生命科学研究部, 助教 (20332869)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 免疫学 / ゲノム / 遺伝子

Research Abstract

Activation-induced cytidine deaminase (AID) is essential to thegeneration for somatic hypermutation at immunoglobulin gene locus. However, it is unclearhow cytoplasmic AID shepherds from cytoplasm to nucleus toward the IgV locus. We studiedthe role of GANP-mediated somatic hypermutation in B cells. We showed that GANP forms acomplex with AID in the cytoplasm and relocated into the nucleus. We found that GANPregulates the recruitment of AID to the immunoglobulin variable regions by modulatingtranscription and nucleosome occupancy.

Research Products

• [Journal Article] GANP regulates recruitment ofAID to immunoglobulin variable regions bymodulating transcription and nucleosomeoccupancy (2013)
  • Author(s): Shailendra Kumar Singh, Kazuhiko Maeda(co-first author), Mohammed Mansour AbbasEid, Sarah Ameen Almofty, Masaya Ono,Phuong Pham, Myron F. Goodman, and NobuoSakaguchi
  • Journal Title: Nat. Commun Volume: 4 Issue: 1 Pages: 1830-1830
  • DOI: 10.1038/ncomms2823
  • Peer Reviewed
• [Journal Article] Dynamic appearance of antigenic epitopes effective for viral neutralization during membrane fusion initiated by interactions between HIV-1 envelope proteins and CD4/CXCR4 (2012)
  • Author(s): Toda T, et al
  • Journal Title: Immunobiology Volume: (印刷中) Issue: 9 Pages: 864-872
  • DOI: 10.1016/j.imbio.2011.12.007
  • Peer Reviewed
• [Journal Article] Molecular Mechanism of Immunoglobulin V-Region Diversification Regulated by Transcription and RNA Metabolism in Antigen-Driven B Cells (2011)
  • Author(s): Sakaguchi N, et al
  • Journal Title: Scandinavian Journal of Immunology Volume: 73 Issue: 6 Pages: 520-526
  • DOI: 10.1111/j.1365-3083.2011.02557.x
  • Peer Reviewed
• [Journal Article] Molecular Mechanism of Immunoglobulin V-Region Diversification Regulated by Transcription and RNA Metabolism in Antigen-Driven B Cells (2011)
  • Author(s): Sakaguchi N, et al.
  • Journal Title: Scandinavian Journal of Immunology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] GANP-mediated recruitment ofactivation-induced cytidine deaminase tocell nuclei and to immunoglobulin variableregion DNA (2010)
  • Author(s): Kazuhiko Maeda, Shailendra KumarSingh, Kazufumi Eda, Masahiro Kitabatake,Phuong Pham, Myron F. Goodman, and NobuoSakaguchi
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 31 Pages: 23945-23953
  • DOI: 10.1074/jbc.m110.131441
  • Peer Reviewed
• [Journal Article] GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region DNA (2010)
  • Author(s): Maeda K, et al.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 23945-23953
  • Peer Reviewed
• [Presentation] GANP associated with HIV-1 RNA export is encapsidated with APOBEC3G into virion core (2012)
  • Author(s): Maeda K
  • Organizer: Keystone Symposia Mutations, Malignancy and Memory-Antibodies and Immunity
  • Place of Presentation: Boston Park Plaza & Towers
  • Year and Date: 2012-03-20
• [Presentation] Role of GANP in transcriptional regulation of immunoglobulin gene locus (2012)
  • Author(s): Sakaguchi N
  • Organizer: Keystone Symposia Mutations, Malignancy and Memory-Antibodies and Immunity
  • Place of Presentation: Boston Park Plaza & Towers
  • Year and Date: 2012-03-20
• [Presentation] Targeting the rearranged immunoglobulin V-region locus in B-cells by the histone acetyl transcriptase activity of GANP (2012)
  • Author(s): Kazuhiko Maeda
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター（東京一ツ橋）
• [Presentation] Mammalian TREX-2 component GANP is involved in HIV-1 mRNA export (2012)
  • Author(s): Kazuhiko Maeda
  • Organizer: The 13th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Aso Resort Grandvrio Hotel
• [Presentation] GANPを介したAPOBEC3Gの抗HIV感染阻止機構の解析 (2012)
  • Author(s): 前田和彦
  • Organizer: 第26回日本エイズ学会学術集会・総会
  • Place of Presentation: 慶応義塾大学 日吉キャンパス
• [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession (2012)
  • Author(s): Kazuhiko Maeda
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] Regulation of immunoglobulin variableregion diversification through GANP-mediated regulation of DNA double-strand break repair machinery (2012)
  • Author(s): Mohammed Mansour Abbas Eid
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] Escorting APOBEC3G toward the fulllength HIV-1 mRNA at the cytoplasmic P bodies (2012)
  • Author(s): Sarah Ameen Almofty
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] GANP regulates APOBEC3G targeting for reduction of HIV-1 infectivity (2012)
  • Author(s): Shailendra Kumar Singh
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe International Conference Center Kobe International Exhibition Hall Kobe Portopia Hotel
• [Presentation] APOBEC3GのHIV-1粒子内への取り込みを制御する宿主因子GANP (2011)
  • Author(s): 前田和彦
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2011-12-01
• [Presentation] Analysis of GANP-associated complex in B-cell nuclei (2011)
  • Author(s): Maeda K
  • Organizer: The 40th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 幕張メッセ、千葉
  • Year and Date: 2011-11-28
• [Presentation] Involvement of GANP in transcriptional regulation of immunoglobulin gene locus (2011)
  • Author(s): Singh SK
  • Organizer: The 40th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 幕張メッセ、千葉
  • Year and Date: 2011-11-28
• [Presentation] GANP augments the immunoglobulin Vregion gene conversion via Ku70 dependent mechanism (2011)
  • Author(s): Eid MMA
  • Organizer: The 40th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 幕張メッセ、千葉
  • Year and Date: 2011-11-28
• [Presentation] GANP promotes APOBEC3G encapsidation in virions to reduce viral infectivity (2011)
  • Author(s): Maeda K
  • Organizer: The 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Aso Resort, Grandvrio Hotel
  • Year and Date: 2011-10-21
• [Presentation] GANP associated with HIV-1 RNA export is encapsidated with Apobec3G into virion cores (2011)
  • Author(s): Maeda K
  • Organizer: The 2011 Meeting on Retroviruses at Cold Spring Harbor Laboratory
  • Place of Presentation: Cold Spring Harbor, New York
  • Year and Date: 2011-05-25
• [Presentation] Transcriptional targeting at immunoglobulin V-region locus by an RNA-export molecule GANP (2011)
  • Author(s): 前田和彦
  • Organizer: 第5回日本エピジェネティクス研究会年会
  • Place of Presentation: KKRホテル熊本、熊本
  • Year and Date: 2011-05-20
• [Presentation] Regulation of immune function by controlling RNA metabolism. The 2nd Workshop of Synthetic Immunology (2010)
  • Author(s): Sakaguchi N, et al.
  • Organizer: The 2nd Workshop of Synthetic Immunology
  • Place of Presentation: Kyoto University Shiran Kaikan, Inamori Hall
  • Year and Date: 2010-12-17
• [Presentation] Apobec3のHIV-1粒子内への取り込みを制御する宿主因子の同定 (2010)
  • Author(s): 阪口薫雄, 他
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪/ザ・プリンスさくらタワー東京
  • Year and Date: 2010-11-24
• [Presentation] GANP is a host factor that regulates Apobec3G encapsidation to HIV-1 viruses (2010)
  • Author(s): Sakaguchi N, et al.
  • Organizer: Asian-African Research Forum 2010
  • Place of Presentation: Melia Hotel, Hanoi
  • Year and Date: 2010-11-11
• [Presentation] GANP-mediated recruitment of AID to the nuclei and to IgV-region DNA (2010)
  • Author(s): Maeda K, et al.
  • Organizer: The 5th International Conference on Gene Regulation in Lymphocyte Development Aegean Conferences
  • Place of Presentation: Minoa Palace Conference Center, Greece
  • Year and Date: 2010-10-09
• [Presentation] GANP regulates the incorporation of Apobec3G into HIV-1 virions (2010)
  • Author(s): Maeda K, et al.
  • Organizer: The 11^<th> Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Hotel Nikko Kumamoto, Aso Resort Grandvrio Hotel
  • Year and Date: 2010-10-06
• [Presentation] GANP controls AID recruitment to immunoglobulin variable region DNA (2010)
  • Author(s): Maeda K, et al.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: The Kobe Convention Center Complex
  • Year and Date: 2010-08-22
• [Presentation] A role of chromatin modification at immunoglobulin locus by GANP (2010)
  • Author(s): Singh SK, et al.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: The Kobe Convention Center Complex
  • Year and Date: 2010-08-22
• [Presentation] Molecular mechanism of immunoglobulin V-region diversification and its application in medical sciences (2010)
  • Author(s): 阪口薫雄, 他
  • Organizer: 日本ヒトプロテオーム機構第8回大会(日本プロテオーム学会2010年会)・第6回日本臨床プロテオーム研究会・連合大会
  • Place of Presentation: 東京ベイホテル東急
  • Year and Date: 2010-07-26
• [Book] 臨床免疫・アレルギー科 (2012)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Book] B細胞の生存維持とmiRNA (2012)
  • Author(s): 前田和彦
  • Publisher: 科学評論社
• [Book] プロテインホスファターゼ2Aの調節と自己免疫 (2012)
  • Author(s): 前田和彦, 他
  • Publisher: 科学評論社
• [Book] 実験医学、免疫記憶の制御と疾患/B 細胞免疫記憶 : 免疫記憶研究のフロンティア (2011)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 羊土社
• [Book] 臨床免疫・アレルギー科 (2011)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Book] 高親和性抗体産生のメカニズム (2011)
  • Author(s): 前田和彦, 他
  • Publisher: 羊土社
• [Book] 胚中心B細胞の分化・増殖とGANP (2011)
  • Author(s): 前田和彦, 他
  • Publisher: 科学評論社
• [Book] 臨床免疫・アレルギー科 (2010)
  • Author(s): 前田和彦、阪口薫雄
  • Publisher: 科学評論社
• [Book] 抗体の抗原親和性成熟とGANPの役割 (2010)
  • Author(s): 前田和彦, 他
  • Publisher: 科学評論社
• [Remarks] 2013年5月15日、熊本日々新聞、「遺伝子変異させ強力な抗体」 ホームページ
  • URL: http://www.k-immu.jp/ja/
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