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Functional analysis of an atypical nuclear small GTPase in the oncogenic signal

Research Project

Project/Area Number 23570166
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionJichi Medical University (2012-2013)
Nara Institute of Science and Technology (2011)

Principal Investigator

TAGO Kenji  自治医科大学, 医学部, 講師 (20306111)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsシグナル伝達 / 発がんシグナル / Gタンパク質 / 低分子量G蛋白質 / シグナル伝達系
Research Abstract

kappaB-Ras is a nuclear-cytoplasmic GTPase that mainly present as GTP-bound form with no stimulating conditions, and its cellular localization is regulated by its bound guanine nucleotides. Here, we found that kappaB-Ras is essential for Ras (G12V)-induced tumorigenesis, although kappaB-Ras itself lacks the oncogenic activities. To clarify the mechanism, by which kappaB-Ras is involved in Ras (G12V)-caused tumorigenesis, we purified the protein complexes including kappaB-Ras2, and identified novel interacting proteins of kappaB-Ras, such as TRB3 and DDB1. TRB3 exhibited the tumor suppressive activity against Ras (G12V). Furthermore, TRB3 induced SUMOylation of kappaB-Ras, and this seems to cause the inhibition of Ras (G12V)-induced transformation. These observations suggest that kappaB-Ras harbors the critical roles in tumorigenesis induced by oncogenic Ras, and this is most likely to be regulated by novel tumor suppressor TRB3 through the SUMOylation of kappaB-Ras.

Report

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

    (32 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (17 results) Remarks (2 results)

  • [Journal Article] Effect of chemical modification on the ability of pyrrolidinium fullerene to induce apoptosis of cells transformed by JAK2 V617F mutant.2014

    • Author(s)
      Funakoshi-Tago M, Tsukada M, Watanabe T, Mameda Y, Tago K, Ohe T, Nakamura S, Mashino T, Kasahara T.
    • Journal Title

      Int Immunopharmacol

      Volume: 20 (1) Issue: 1 Pages: 258-263

    • DOI

      10.1016/j.intimp.2014.02.035

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5.2014

    • Author(s)
      Tago K, Funakoshi-Tago M, Itoh H, Furukawa Y, Kikuchi J, Kato T, Suzuki K, Yanagisawa K
    • Journal Title

      Oncogene

      Volume: 未定 Issue: 3 Pages: 310-318

    • DOI

      10.1038/onc.2013.561

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: Involvement of Ric-8B in Gs suppression by Gq signal2013

    • Author(s)
      Riris Jenie, Motoki Nishimura, Mika Fujino, Michio Nakaya, Norikazu Mizuno, Kenji Tago, Hitoshi Kurose & Hiroshi Itoh.
    • Journal Title

      Genes to Cells

      Volume: 18 Issue: 12 Pages: 1095-1106

    • DOI

      10.1111/gtc.12099

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of FANCC in JAK2 V617F mutant-induced resistance to DNA cross-linking drugs.2013

    • Author(s)
      Ueda F, Sumi K, Tago K, Kasahara T, Funakoshi-Tago M
    • Journal Title

      Cell Signal

      Volume: 25 (11) Issue: 11 Pages: 2115-2124

    • DOI

      10.1016/j.cellsig.2013.07.003

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical roles of Myc-ODC axis in the cellular transformation induced by myeloproliferative neoplasm-associated JAK2 V617F mutant.2013

    • Author(s)
      Funakoshi-Tago M, Sumi K, Kasahara T, Tago K.
    • Journal Title

      PLoS One.

      Volume: 8 (1) Issue: 1 Pages: e52844-e52844

    • DOI

      10.1371/journal.pone.0052844

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rab33a mediates anterograde vesicular transport for membrane exocytosis and axon outgrowth2012

    • Author(s)
      Nakazawa H, Sada T, Toriyama M, Tago K, Sugiura T, Fukuda M, Inagaki N.
    • Journal Title

      J Neurosci.

      Volume: 32(37) Pages: 12712-12725

    • NAID

      120005716799

    • Related Report
      2013 Final Research Report
  • [Journal Article] Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration2012

    • Author(s)
      Toriyama M, Mizuno N, Fukami T, Iguchi T, Toriyama M, Tago K, Itoh H
    • Journal Title

      J. Biol Chem

      Volume: 287 Issue: 16 Pages: 12691-12702

    • DOI

      10.1074/jbc.m111.316307

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fullerene derivative prevents cellular transformation induced by JAK2 V617F mutant through inhibiting c-Jun N-terminal kinase pathway.2012

    • Author(s)
      Funakoshi-Tago M, Nagata T, Tago K, Tsukada M, Tanaka K, Nakamura S, Mashino T, Kasahara T.
    • Journal Title

      Cell Signal.

      Volume: 24 (11) Issue: 11 Pages: 2024-2034

    • DOI

      10.1016/j.cellsig.2012.06.014

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rab33a mediates anterograde vesicular transport for membrane exocytosis and axon outgrowth.2012

    • Author(s)
      Nakazawa H, Sada T, Toriyama M, Tago K, Sugiura T, Fukuda M, Inagaki N.
    • Journal Title

      J Neurosci.

      Volume: 32 (37) Pages: 12712-12725

    • NAID

      120005716799

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells2011

    • Author(s)
      Sumi K, Tago K, Kasahara T, Funakoshi-Tago M.
    • Journal Title

      FEBS Lett.

      Volume: 585(12) Issue: 12 Pages: 1884-1890

    • DOI

      10.1016/j.febslet.2011.04.068

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin2011

    • Author(s)
      Funakoshi-Tago M., et al
    • Journal Title

      Int.Immunopharmacol.

      Volume: 11 Issue: 9 Pages: 1150-1159

    • DOI

      10.1016/j.intimp.2011.03.012

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Akt activation through the phosphorylation of erythropoietin receptor at tyrosine 479 is required for myeloproliferative disorder-associated JAK2 V617F mutant-induced cellular transformation2011

    • Author(s)
      Kamishimoto J, et al
    • Journal Title

      Cell.Signal.

      Volume: 23 Issue: 5 Pages: 849-856

    • DOI

      10.1016/j.cellsig.2011.01.009

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] JAK2 is an important signal transducer in IL-33-induced NF-κB activation.2011

    • Author(s)
      Funakoshi-Tago, M., Tago, K., Sato, Y., Tominaga, S., and Kasahara, T.
    • Journal Title

      Cell. Signal

      Volume: 23 Issue: 2 Pages: 363-370

    • DOI

      10.1016/j.cellsig.2010.10.006

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 核内におけるIL-33の機能解析2013

    • Author(s)
      太田聡, 多胡憲治, 多胡めぐみ, 松儀実広, 柳澤健
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] がん化型Ras変異体が誘起する発がんシグナルはTNFαによるNF-κBの活性化を増強する2013

    • Author(s)
      多胡憲治, 多胡めぐみ, 太田聡, 松儀実広, 柳澤健
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 心筋細胞のGタンパク質シグナルにおけるRic-8Bの機能2013

    • Author(s)
      Riris I. Jenie, 仲矢道雄, 水野憲一, 多胡憲治, 黒瀬等, 伊東広
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] がん抑制遺伝子産物Arfはc‐MycとDDX5により構成されるポジティブフィードバックループを抑制する2012

    • Author(s)
      多胡憲治, 多胡めぐみ, 伊東広, 古川雄祐, 菊池次郎, 加藤高晴, 鈴木浩一, 柳澤健
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞のがん化におけるIL-33の役割の解析2012

    • Author(s)
      太田聡, 多胡憲治, 多胡めぐみ, 松儀実広, 柳澤健
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 低分子量G蛋白質κB-RasはTRB3およびDDB1と結合して発がんシグナルに関与する2012

    • Author(s)
      多胡憲治, 多胡めぐみ, 柳澤健, 杉山直之, 冨田勝, 水野憲一, 伊東広
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 慢性骨髄増殖性腫瘍由来JAK2変異体のがん化シグナルにおけるc-Myc-ODC経路の役割2012

    • Author(s)
      多胡めぐみ, 鷲見和也, 多胡憲治, 笠原忠
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 低分子量G蛋白質κB-RasはTRB3およびDDB1と結合して発がんシグナルに関与する2012

    • Author(s)
      多胡 憲治, 多胡 めぐみ, 柳澤 健, 杉山直之, 冨田 勝, 水野 憲一, 伊東 広
    • Organizer
      第85回 日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] がん抑制遺伝子産物Arfはc-MycとDDX5により構成されるポジティブフィードバックループを抑制する2012

    • Author(s)
      多胡 憲治, 多胡 めぐみ, 伊東 広, 古川 雄祐, 菊池 次郎, 加藤 高晴, 鈴木 浩一, 柳澤 健
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional involvement of an atypical nuclear-cytoplasmic small GTPaseκB-Ras in oncogenic signaling pathway2011

    • Author(s)
      多胡憲治, 多胡めぐみ, 深尾陽一朗, 杉山直之, 冨田勝, 水野憲一, 伊東広
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Gタンパク質シグナルにより制御されるSUMO化とその分子機構の解析2011

    • Author(s)
      多胡憲治, 多胡めぐみ, Susanna Chiocca, 水野憲一, 伊東広
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 微小管結合タンパク質doublecortinのPKAによるリン酸化を介した新規アクチン骨格制御2011

    • Author(s)
      鳥山真奈美, 猪口徳一, 深見岳史, 多胡憲治, 水野憲一, 伊東広
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Gタンパク質シグナルにより制御されるSUMO化とその分子機構の解析2011

    • Author(s)
      多胡憲治、多胡めぐみ、Susanna Chiocca、水野憲一、伊東広
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Research-status Report
  • [Presentation] Functional involvement of an atypical nuclear-cytoplasmic small GTPase κB-Ras in oncogenic signaling pathway2011

    • Author(s)
      多胡憲治、多胡めぐみ、深尾陽一、杉山直幸、冨田勝、水野憲一、伊東広
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] がん化型Ras変異体が誘起する発がんシグナルはTNFαによるNF-κBの活性化を増強する

    • Author(s)
      多胡憲治、多胡めぐみ、太田聡、松儀実広、柳澤健
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 心筋細胞のGタンパク質シグナルにおけるRic-8Bの機能

    • Author(s)
      Riris I. Jenie、仲矢 道雄、水野 憲一、多胡 憲治、黒瀬 等、伊東 広
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 核内におけるIL-33の機能解析

    • Author(s)
      太田聡、多胡憲治、多胡めぐみ、松儀実広、柳澤健
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/biochem/kozo/Structural_Biochem/HOME.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 構造生化学

    • URL

      http://www.jichi.ac.jp/biochem/kozo/Structural_Biochem/HOME.html

    • Related Report
      2013 Annual Research Report

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

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