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Relationship between autophagy regulation by SIRT2 and its spindle assembly checkpoint function

Research Project

Project/Area Number 23570005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionTottori University

Principal Investigator

INOUE Toshiaki  鳥取大学, 医学部, 准教授 (80305573)

Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー / SIRT2 / 紡錘体チェックポイント / 微小管阻害剤 / 分裂死 / 四倍体 / 中心体
Outline of Final Research Achievements

We previously identified SIRT2, a member of the sirtuin protein family, as a regulator of turning of SAC activation. We investigated whether SIRT2 regulates basal autophagy and whether it is mediated by centrosome function since SIRT2 knockdown cells exhibited the centrosome fragmentation during SAC cause by the exposure to microtubule inhibitors. We show, by combined knockdown of autophagy genes and SIRT2, that SIRT2 serves this function at least partially by suppressing basal autophagy levels. However, the centrosome function is not involved in this function. Alternatively, we identified a possible pathway that mediates SAC-Off and the subsequent cell death among autophagy-regulated pathways and independently a cell cycle regulator. To delineate the relationship among autophagy and the regulatory pathway will lead to precise understanding of mechanism of SAC-Off and the subsequent cell death, which will increase the efficacy of microtubule inhibitors on tumor therapy.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 2 results,  Open Access: 4 results) Presentation (9 results) Book (2 results) Remarks (8 results)

  • [Journal Article] A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.2015

    • Author(s)
      Oshimura Mitsuo, Uno Narumi, Kazuki Yasuhiro, Katoh Motonobu, Inoue Toshiaki
    • Journal Title

      Chromosome Res.

      Volume: 23 Issue: 1 Pages: 111-133

    • DOI

      10.1007/s10577-014-9459-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrent Micronucleation through Cell Cycle Progression in the Presence of Microtubule Inhibitors2015

    • Author(s)
      Nakayama Yuji, Uno Narumi, Uno Katsuhiro, Mizoguchi Yamato, Komoto Shinya, Kazuki Yasuhiro, Nanba Eiji, Inoue Toshiaki, Oshimura Mitsuo
    • Journal Title

      Cell Structure and Function

      Volume: 40 Issue: 1 Pages: 51-59

    • DOI

      10.1247/csf.14005

    • NAID

      130004885868

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Construction of a luciferase reporter system to monitor osteogenic differentiation of mesenchymal stem cells by using a mammalian artificial chromosome vector.2015

    • Author(s)
      Narai Takashi, Katoh Motonobu, Inoue Toshiaki, Taniguchi Makoto, Kazuki Kanako, Kazuki Yasuhiro, Sato Kenzo, Kodani Isamu, Ryoke Kazuo, Oshimura Mitsuo
    • Journal Title

      Yonago Acta Med.

      Volume: 58

    • NAID

      120005596729

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIRT2 knockdown increases basal autophagy and prevents post-slippage death by abnormally prolonging the mitotic arrest that is induced by microtubule inhibitors.2014

    • Author(s)
      Inoue Toshiaki, Nakayama Yuji, Li Yanze, Matsumori Haruka, Takahashi Haruka, Kojima Hirotada, Wanibuchi Hideki, Katoh Motonobu, Oshimura Mitsuo
    • Journal Title

      FEBS J.

      Volume: 281 Issue: 11 Pages: 2623-2637

    • DOI

      10.1111/febs.12810

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition.2014

    • Author(s)
      Suematsu Tomohisa, Li Yanze, Kojima Hirotada, Nakajima Koichi, Oshimura Mitsuo, Inoue Toshiaki
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 453 Issue: 3 Pages: 588-594

    • DOI

      10.1016/j.bbrc.2014.09.128

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down-regulates its enzymatic activity2014

    • Author(s)
      Tsusaka Takeshi, Guo Tingting, Yagura Teiti, Inoue Toshiaki, Yokode Masayuki, Inagaki Nobuya, Kondoh Hiroshi
    • Journal Title

      Genes Cells

      Volume: 19 Issue: 10 Pages: 766-777

    • DOI

      10.1111/gtc.12176

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIRT2 knockdown increases basal autophagy and prevents post-slippage death by abnormally prolonging the mitotic arrest that is induced by microtubule inhibitors2014

    • Author(s)
      Inoue, Toshiaki; Nakayama, Yuji; Li, Yanze; Matsumori, Haruka; Takahashi, Haruka; Kojima, Hirotada; Wanibuchi, Hideki; Katoh, Motonobu; Oshimura, Mitsuo
    • Journal Title

      FEBS J

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-6-STAT3 signaling and premature senescence.2013

    • Author(s)
      Kojima H, Inoue T, Kunimoto H, Nakajima K
    • Journal Title

      JAK-STAT

      Volume: 2

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The STAT3-IGFBP5 axis is critical for IL-6/gp130-induced premature senescence in human fibroblasts2012

    • Author(s)
      Kojima H, Kunimoto H, Inoue T, Nakajima K
    • Journal Title

      Cell Cycle

      Volume: 11 Issue: 4 Pages: 730-739

    • DOI

      10.4161/cc.11.4.19172

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-143 Regulates Human Osteosarcoma Metastasis by Regulating Matrix Metalloprotease-13 Expression2011

    • Author(s)
      Osaki M, Takeshita F, Sugimoto Y, Kosaka N, Yamamoto Y, Yoshioka Y, Kobayashi E, Yamada T, Kawai A, Inoue T, Ito H, Oshimura M, Ochiya T
    • Journal Title

      Molecular Therapy

      Volume: 19(6) Issue: 6 Pages: 1123-1130

    • DOI

      10.1038/mt.2011.53

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of PITX1 as a TERT suppressor gene located on human chromosome 52011

    • Author(s)
      Qi DL, Ohhira T, Fujisaki C, Inoue T, Ohta T, Osaki M, Ohshiro E, Seko T, Aoki S, Oshimura M & Kugoh H
    • Journal Title

      Mol. Cell Biol

      Volume: 31(8) Issue: 8 Pages: 1624-1636

    • DOI

      10.1128/mcb.00470-10

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] オートファジー制御による四倍体からの細胞死誘導経路2014

    • Author(s)
      足立美保子、末松知久、押村光雄、井上敏昭
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] SIRT2によるオートファジー異常亢進の抑制は微小管阻害剤処理による癌の効的な癌細胞死誘導に必要である2013

    • Author(s)
      井上敏昭、李艶沢、押村光雄
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Searching for target molecules for deacetylation by SIRT2 during mitotic slippage caused by microtubule inhibitors2013

    • Author(s)
      Tomohisa Suematsu, Yanze Li, Mitsuo Oshimura, Toshiaki Inoue
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] 複数の遺伝子搭載が可能な人工染色体ベクターの構築2012

    • Author(s)
      荻野由加利、中山祐二、松森はるか、田中伸幸、押村光雄、難波栄ニ、井上敏昭
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 松知久、李艶澤、中山祐二、押村光雄、井上敏昭2012

    • Author(s)
      分裂期でのSIRT2脱アセチル化標的タンパクの探索
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 吉川なつこ、末松知久、大平崇人、押村光雄、久郷裕之、井上敏昭2012

    • Author(s)
      hTERT発現を抑制するPitX1から解き明かすhTERT発現制御ネットワーク
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 複数の遺伝子搭載が可能な人工染色体ベクターの構築2011

    • Author(s)
      荻野由加利、松森はるか、押村光雄、中山祐二、井上敏昭
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2011 Research-status Report
  • [Presentation] がん治療の新たな標的分子としてのSIRT22011

    • Author(s)
      李艶沢、末松知久、中山祐二、押村光雄、井上敏昭
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2011 Research-status Report
  • [Presentation] 麻疹ウイルスエンベロープタンパク質を利用したヒト人工染色体ベクターのin vivo導入に向けた試み2011

    • Author(s)
      高橋悠、加藤基伸、尾崎充彦、中山祐二、中村貴史、井上敏昭、押村光雄
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2011 Research-status Report
  • [Book] Interleukin-6 Induces Premature Senescence Involving the STAT3 and Insulin-Like Growth Factor-Binding Protein 5.2014

    • Author(s)
      Kojima Hirotada, Kunimoto Hiroyuki, Inoue Toshiaki, Nakajima Koichi
    • Total Pages
      8
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Aging, Cancer, and Noncancer Pathologies, Interleukin-6 Induces Premature Senescence Involving the STAT3 and Insulin-Like Growth Factor-Binding Protein 5. TUMOR DORMANCY AND CELLULAR QUIESCENCE AND SENESCENCEM.2013

    • Author(s)
      Kojima H, Kunimoto H, Inoue T, Nakajima K
    • Publisher
      Springer
    • Related Report
      2012 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科ゲノム医工学分野ホームページ

    • URL

      https://www.facebook.com/genoiko

    • Related Report
      2014 Annual Research Report
  • [Remarks] 鳥取大学 染色体工学研究センターホームページ

    • URL

      http://www.med.tottori-u.ac.jp/chromosome/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 鳥取大学医学部生命科学科 ゲノム医工学分野ホームページ

    • URL

      https://www.facebook.com/genoiko

    • Related Report
      2013 Research-status Report
  • [Remarks] 鳥取大学染色体工学研究センターホームページ

    • URL

      http://www.med.tottori-u.ac.jp/chromosome/

    • Related Report
      2013 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科ゲノム医工学分野ホームページ

    • URL

      http://www.med.tottori-u.ac.jp/genome/

    • Related Report
      2012 Research-status Report
  • [Remarks] 鳥取大学染色体工学研究センターホームページ

    • URL

      http://www.med.tottori-u.ac.jp/chromosome/

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.tottori-u.ac.jp/genome/309/

    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.med.tottori-u.ac.jp/chromosome/1233.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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