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2013 Fiscal Year Final Research Report

Roles of impairment of centrosome maturation in leukemogenesis

Research Project

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Project/Area Number 23390253
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHiroshima University

Principal Investigator

INABA Toshiya  広島大学, 原爆放射線医科学研究所, 教授 (60281292)

Co-Investigator(Kenkyū-buntansha) HONDA Hiroaki  広島大学, 原爆放射線医科学研究所, 教授 (40245064)
MATSUI Hirotaka  広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords中心体 / 分裂異常 / 骨髄系腫瘍 / モノソミー7
Research Abstract

During prometaphase, dense microtubule nucleation sites at centrosomes form robustspindles that align chromosomes promptly. Failure of centrosome maturation leaves chromosomes scattered, as seen in cancer cells, including myelodysplastic syndrome (MDS).We previously reported that the Miki (LOC253012) gene is frequently deleted in MDS patients, and that low levels of Miki are associated with abnormal mitosis. Here we demonstrate that Miki localizes to the Golgi apparatus and is poly (ADP-ribosyl)ated by tankyrase-1 during late G2 and prophase. PARsylated Miki then translocates to mitotic centrosomes and anchors CG-NAP, a large scaffold protein of the g-tubulin ring complex . Due to impairment of microtubule aster formation, cells in which tankyrase-1, Miki, or CG-NAP expression is downregulated all show prometaphase disturbance, scattered and lagging chromosomes. Our data suggest that PARsylation of Miki by tankyrase-1 is a key initial event promoting prometaphase.

  • Research Products

    (10 results)

All 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (6 results)

  • [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function2014

    • Author(s)
      Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
    • Journal Title

      PLOS ONE

      Volume: 9 Pages: e87425

    • Peer Reviewed
  • [Journal Article] MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters2014

    • Author(s)
      Okuda H, Kawaguchi M, Kanai A, Matsui H, Kawamura T, Inaba T, Kitabayashi I, Yokoyama A
    • Journal Title

      Nucleic Acids Res

      Volume: 42 Pages: 4241-4256

    • Peer Reviewed
  • [Journal Article] Combination therapies with NS5A, NS3 and NS5B inhibitors on different genotypes of hepatitis C virus in human hepatocyte chimeric mice2013

    • Author(s)
      Shi N, Hiraga N, Imamura M, Hayes CN, Zang Y, Kosaka K, Ozaka K, Okazaki A, Murakami E, Tsuge M, Abe H, Aikata H, Takahashi S, Ochi H, Tateno-Mukaidani C, Yoshizato K, Matsui H, Kanai A, Inaba T, McPhee F, Gao M, Chayama K
    • Journal Title

      Gut

      Volume: 62 Pages: 1055-1061

    • Peer Reviewed
  • [Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 72013

    • Author(s)
      Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Takubo K, Suda T, Nakamura T, Wolff L, Honda H, Inaba T
    • Journal Title

      Cancer Cell

      Volume: 24 Pages: 305-317

    • Peer Reviewed
  • [Presentation] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, in mice induces the development of myeloid malignancies mimicking human disease with monosomy 72013

    • Author(s)
      Matsui H
    • Organizer
      ASH
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      20131207-10
  • [Presentation] 造血器悪性腫瘍の発症・進展におけるエピゲノム異常の関与2013

    • Author(s)
      松井啓隆
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      ホテルクラウンパレス青森
    • Year and Date
      20131018-20
  • [Presentation] Samd9L-deficient mice develop myeloid malignancies mimicking human diseases with Monosomy 72013

    • Author(s)
      Nagamachi A
    • Organizer
      第75回日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      20131011-13
  • [Presentation] Chromosomal instability due to downregulation of Miki, a del(7q) -responsible gene product2013

    • Author(s)
      Ozaki Y
    • Organizer
      第75回日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      20131011-13
  • [Presentation] 次世代シーケンサーによる一塩基単位での5ハイドロキシメチルシトシンの解析法確立と造血器腫瘍での定量2013

    • Author(s)
      松井啓隆
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20131003-05
  • [Presentation] NF-κBに対するユビキチン修飾酵素A20はアポトーシスと炎症の抑制により成体造血の恒常性維持に重要な役割を果たす2013

    • Author(s)
      長町安希子
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20131003-05

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Published: 2015-06-25  

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