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2013 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number 23390122
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKumamoto University

Principal Investigator

SAKAGUCHI NOBUO  熊本大学, 生命科学研究部, 教授 (70192086)

Project Period (FY) 2011-04-01 – 2014-03-31
Keywords免疫学 / ゲノム / 遺伝子
Research Abstract

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.

  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (11 results) Book (7 results) Remarks (1 results)

  • [Journal Article] GANP regulates the choice of DNA repair pathway by DNA-PKcs interaction in AID-dependent IgV region diversification2014

    • Author(s)
      Eid MMA, Maeda K (co-first author), Almofty SA, Singh SK, Shimoda M, Sakaguchi N
    • Journal Title

      J. Immunol

      Volume: 192(in press)

    • DOI

      10.4049/jimmunol.1400021

    • Peer Reviewed
  • [Journal Article] Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability2014

    • Author(s)
      Ye B, Dai Z, Liu B, Wang R, Li C, Huang G, Wang S, Xia P, Yang X, Kuwahara K, Sakaguchi N, Fan Z
    • Journal Title

      Stem Cells

      Volume: 32 Pages: 623-635

    • DOI

      10.1002/stem.1580

    • Peer Reviewed
  • [Journal Article] Infection of adult thymus with murine retrovirus induces virus-specific central tolerance that prevents functional memory CD8+ T cell differentiation2014

    • Author(s)
      Takamura S, Kajiwara E, Tsuji-Kawahara S, Masumoto T, Fujisawa M, Kato M, Chikaishi T, Kawasaki Y, Kinoshita S, Itoi M, Sakaguchi N, Miyazawa M
    • Journal Title

      PLoS Pathog

      Volume: 10 Pages: e1003937

    • DOI

      10.1371/journal.ppat.1003937

    • Peer Reviewed
  • [Journal Article] Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus2013

    • Author(s)
      Ogiwara H, Yasui F, Munekata K, Takagi-Kamiya A, Munakata T, Nomura N, Shibasaki F, Kuwahara K, Sakaguchi N, Sakoda Y, Kida H, Kohara M
    • Journal Title

      Am. J. Pathol

      Volume: 184 Pages: 171-183

    • DOI

      10.1016/j.ajpath.2013.10.004

    • Peer Reviewed
  • [Journal Article] CA-S27 : a novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma2013

    • Author(s)
      Silsirivanit A, Araki N, Wongkham C, Vaeteewoottacharn K, Pairojkul C, Kuwahara K, Narimatsu Y, Sawaki H, Narimatsu H, Okada S, Sakaguchi N, Wongkham S
    • Journal Title

      Cancer Sci

      Volume: 104 Pages: 1278-1284

    • DOI

      10.1111/cas.12222

    • Peer Reviewed
  • [Journal Article] Broad-spectrum detection of h5 subtype influenza a viruses with a new fluorescent immunochromatography system2013

    • Author(s)
      Sakurai A, Takayama K, Nomura N, Munakata T, Yamamoto N, Tamura T, Yamada J, Hashimoto M, Kuwahara K, Sakoda Y, Suda Y, Kobayashi Y, Sakaguchi N, Kida H, Kohara M, Shibasaki F
    • Journal Title

      PLoS One

      Volume: 8 Pages: e76753

    • DOI

      10.1371/journal.pone.0076753

    • Peer Reviewed
  • [Journal Article] Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival2013

    • Author(s)
      Rezano A, Kuwahara K, Yamamoto-Ibusuki M, Kitabatake M, Moolthiya P, Phimsen S, Suda T, Tone S, Yamamoto Y, Iwase H, Sakaguchi N
    • Journal Title

      BMC Cancer

      Volume: 13 Pages: 562

    • DOI

      10.1186/1471-2407-13-562

    • Peer Reviewed
  • [Journal Article] GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity2013

    • Author(s)
      Maeda K, Almofty SA (co-first author), Singh SK, Eid MMA, Shimoda M, Ikeda T, Koito A, Pham P, Goodman MF, Sakaguchi N
    • Journal Title

      J. Immunol

      Volume: 191 Pages: 6030-6039

    • DOI

      10.4049/jimmunol.1302057

    • Peer Reviewed
  • [Journal Article] GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy2013

    • Author(s)
      Singh SK, Maeda K (co-first author), Eid MMA, Almofty SA, Ono M, Pham P, Goodman MF, Sakaguchi N
    • Journal Title

      Nat. Commun

      Volume: 4 Pages: 1830

    • DOI

      10.1038/ncomms2823

    • Peer Reviewed
  • [Journal Article] Lyn signaling to upregulate GANP is critical for the survival of high-affinity B cells in germinal centers of lymphoid organs2012

    • Author(s)
      Kuwahara K, Nakaya T, Phimsen S, Toda T, Kitabatake M, Kaji T, Takemori T, Watanabe T, Sakaguchi N
    • Journal Title

      J. Immunol

      Volume: 189 Pages: 3472-3479

    • DOI

      10.4049/jimmunol.1200649

    • Peer Reviewed
  • [Journal Article] Transgenic overexpression of G5PR that is normally augmented in centrocytes impairs the enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice2012

    • Author(s)
      Kitabatake M, Toda T, Kuwahara K, Igarashi H, Ohtsuji M, Tsurui H, Hirose S, Sakaguchi N
    • Journal Title

      J. Immunol

      Volume: 189 Pages: 1193-1201

    • DOI

      10.4049/jimmunol.1102774

    • 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/CXCR42012

    • Author(s)
      Toda T, Kuwahara K, Kondo N, Matsuda Z, Maeda Y, Maeda K, Sakaguchi N
    • Journal Title

      Immunobiology

      Volume: 217 Pages: 864-872

    • DOI

      10.1016/j.imbio.2011.12.007

    • Peer Reviewed
  • [Journal Article] A novel serum carbohydrate marker on mucin 5AC : values for diagnostic and prognostic indicators for cholangiocarcinoma2011

    • Author(s)
      Silsirivanit A, Araki N, Wongkham C, Pairojkul C, Narimatsu Y, Kuwahara K, Narimatsu H, Wongkham S, Sakaguchi N
    • Journal Title

      Cancer

      Volume: 117 Pages: 3393-403

    • DOI

      10.1002/cncr.25912

    • Peer Reviewed
  • [Journal Article] Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP2011

    • Author(s)
      Phimsen S, Kuwahara K, Nakaya T, Ohta K, Suda T, Rezano A, Kitabatake M, Vaeteewoottacharn K, Okada S, Tone S, Sakaguchi N
    • Journal Title

      Apoptosis

      Volume: 17 Pages: 679-690

    • DOI

      10.1007/s10495-012-0711-8

    • Peer Reviewed
  • [Journal Article] Molecular mechanism of immunoglobulin V-region diversification regulated by transcription and RNA metabolism in antigen-driven B cells2011

    • Author(s)
      Sakaguchi N, Maeda K, Kuwahara K
    • Journal Title

      Scand. J. Immunol

      Volume: 73 Pages: 520-526

    • DOI

      10.1111/j.1365-3083.2011.02557.x

    • Peer Reviewed
  • [Presentation] GANP plays a regulatory role in the choice of DNA repair pathway by dissociating DNA-PKcs in AID-induced immunoglobulin V-region diversification2014

    • Author(s)
      Sakaguchi N, Eid MMA, Singh SK, Almofty SA, Shimoda M, Maeda K
    • Organizer
      Keystone Symposia Conference Biology of B Cell Responses
    • Place of Presentation
      Keystone Conference Center (コロラド, アメリカ)
    • Year and Date
      2014-02-13
  • [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession2013

    • Author(s)
      Maeda K, Singh SK, Eid MMA, Almofty SA, Shimoda M, Kawabata T, Sakaguchi N
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2013-12-13
  • [Presentation] B cell-associated regulation of DNA repair pathway through interaction with DNA-PKcs in IgV-region diversification2013

    • Author(s)
      Eid MMA, Maeda K, Almofty SA, Singh SK, Shimoda M, Sakaguchi N
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2013-12-13
  • [Presentation] GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession2012

    • Author(s)
      Maeda K, Singh SK, Almofty SA, Eid MMA, Shimoda M, Sakaguchi N
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場, 神戸国際展示場, 神戸ポートピアホテル(兵庫)
    • Year and Date
      2012-12-05
  • [Presentation] Regulation of immunoglobulin variable region diversification through GANP-mediated regulation of DNA double-strand break repair machinery2012

    • Author(s)
      Eid MMA, Maeda K, Singh SK, Almofty SA, Shimoda M, Sakaguchi N
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場, 神戸国際展示場, 神戸ポートピアホテル(兵庫)
    • Year and Date
      2012-12-05
  • [Presentation] Targeting the rearranged immunoglobulin V-region locus in B-cells by the histone acetyl transcriptase activity of GANP2012

    • Author(s)
      Maeda K, Singh SK, Almofty SA, Eid MMA, Ono M, Sakaguchi N
    • 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)
    • Year and Date
      2012-05-14
  • [Presentation] Role of GANP in transcriptional regulation of immunoglobulin gene locus2012

    • Author(s)
      Sakaguchi N, Singh SK, Almofty SA, Eid MMA, Ono M, Maeda K
    • Organizer
      Keystone Symposia Mutations, Malignancy and Memory-Antibodies and Immunity
    • Place of Presentation
      Boston, Boston Park Plaza & Towers (ボストン, アメリカ)
    • Year and Date
      2012-03-21
  • [Presentation] Analysis of GANP-associated complex in B-cell nuclei2011

    • Author(s)
      Maeda K, Singh SK, Almofty SA, Eid MMA, Sakaguchi N
    • Organizer
      第40回日本免疫学会学術集会
    • 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 locus2011

    • Author(s)
      Singh SK, Maeda K, Almofty SA, Eid MMA, Sakaguchi N
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2011-11-28
  • [Presentation] GANP augments the immunoglobulin V region gene conversion via Ku70 dependent mechanism2011

    • Author(s)
      Eid MMA, Maeda K, Singh SK, Almofty SA, Sakaguchi N
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2011-11-28
  • [Presentation] Transcriptional targeting at immunoglobulin V-region locus by an RNA-export molecule GANP2011

    • Author(s)
      Maeda K, Singh SK, Almofty SA, Eid MAA, Sakaguchi N
    • 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
  • [Book] 臨床免疫・アレルギー科, 免疫グロブリンの体細胞高頻度突然変異誘導と GANP2014

    • Author(s)
      下田真唯子, 前田和彦, 阪口薫雄
    • Total Pages
      472-479
    • Publisher
      科学評論社
  • [Book] 臨床免疫・アレルギー科, 胚中心B細胞の高親和性成熟における GANP の役割2013

    • Author(s)
      前田和彦, 阪口薫雄
    • Total Pages
      115-121
    • Publisher
      科学評論社
  • [Book] 臨床免疫・アレルギー科, B細胞の生存維持とmiRNA2012

    • Author(s)
      前田和彦, 阪口薫雄
    • Total Pages
      251-258
    • Publisher
      科学評論社
  • [Book] 免疫学コア講義改訂3版2012

    • Author(s)
      阪口薫雄, 前田和彦
    • Publisher
      南山堂
  • [Book] 臨床免疫・アレルギー科, 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, 阪口薫雄
    • Total Pages
      119-124
    • Publisher
      科学評論社
  • [Book] 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, 実験医学, 高親和性抗体産生のメカニズム2011

    • Author(s)
      前田和彦, 阪口薫雄
    • Total Pages
      106-111
    • Publisher
      羊土社
  • [Book] 臨床免疫・アレルギー科, 胚中心B細胞の分化・増殖と GANP2011

    • Author(s)
      前田和彦, 阪口薫雄
    • Total Pages
      109-115
    • Publisher
      科学評論社
  • [Remarks] 新聞報道2013年5月15日, 熊本日日新聞, 「遺伝子変異させ強力な抗体」

    • URL

      http://www.k-immu.jp/ja/

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Published: 2015-06-25  

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