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Targeting Mnk/eIF4E pathway for cancer therapy

Research Project

Project/Area Number 23590364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionHiroshima University

Principal Investigator

UEDA Takeshi  広島大学, 原爆放射線医科学研究所, 助教 (60585149)

Co-Investigator(Kenkyū-buntansha) HONDA Hiroaki  広島大学, 原爆放射線医科学研究所, 教授 (40245064)
FUKUNAGA Rikiro  大阪薬科大学, 薬学部, 教授 (40189965)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsシグナル伝達 / 翻訳制御
Research Abstract

MAP kinase-interacting kinase 1 (Mnk1) and Mnk2 are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate a translation initiation factor eIF4E. We have previously reported that Mnk1/2 double deficiency delays tumor development in a mouse lymphoma model and that suppression of Mnk1 significantly reduces the tumorigenic activity of xenografted human glioma cells. To further investigate the regulatory network of Mnks, we attempted to search for Mnk1- interacting proteins. The Flag-tagged wild-type Mnk1 and kinase-dead Mnk1 complexes were affinity-purified from mouse embryonic fibroblasts, and then the identities of binding proteins were determined by tandem mass spectrometry. As a result, a 130kDa deubiquitinase was identified as a novel Mnk1-binding partner. We are currently exploring the impact of the interaction between these proteins.

Report

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

    (19 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (7 results)

  • [Journal Article] Interplay between chromatin-modifying enzymes controls colon cancer progression through Wnt signaling2014

    • Author(s)
      Chevillard-Briet M, Quaranta M, Grézy A, Mattera L, Courilleau C, Philippe M, Mercier P, Corpet D, Lough J, Ueda T, Fukunaga R, Trouche D, Escaffit F
    • Journal Title

      Hum Mol Genet

      Volume: 23(8) Pages: 2120-2131

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [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 Z, Takubo K, Suda T, Oda H, Inaba T, Honda H
    • Journal Title

      PLoS On

      Volume: 9(1)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model2013

    • Author(s)
      Berger T, Ueda T, Arpaia E, Chio II, Shirdel EA, Jurisica I, Hamada K, You-Ten A, Haight J, Wakeham A, Cheung CC, Mak TW
    • Journal Title

      Oncogene

      Volume: 32(41) Pages: 4989-4994

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p152013

    • Author(s)
      Inoue S, Hao Z, Elia AJ, Cescon D, Zhou L, Silvester J, Snow B, Harris IS, Sasaki M, Li WY, Itsumi M, Yamamoto K, Ueda T, Dominguez-Brauer C, Gorrini C, Chio II, Haight J, You-Ten A, McCracken S, Wakeham A, Ghazarian D, Penn LJ, Melino G, Mak TW
    • Journal Title

      Genes Dev

      Volume: 27(10) Pages: 1101-11114

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CIZ1, a p21 (Cip1/Waf1) -interacting protein, functions as a tumor suppressor in vivo2013

    • Author(s)
      Nishibe R, Watanabe W, Ueda T, Yamasaki N, Koller R, Wolff L, Honda Z, Ohtsubo M, Honda H
    • Journal Title

      FEBS Lett

      Volume: 587(10) Pages: 1529-1535

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells2013

    • Author(s)
      Gorentla BK, Krishna S., Shin J., Inoue M., Shinohara ML, Grayson JM, Fukunaga R, Zhong XP
    • Journal Title

      J Immunol

      Volume: 190(3) Pages: 1026-1037

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells2013

    • Author(s)
      Shi Y, Frost P, Hoang B, Yang Y, Fukunaga R, Gera J, Lichtenstein A
    • Journal Title

      Oncogene

      Volume: 32(2) Pages: 190-197

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sprouty proteins are negative regulators of interferon (IFN)-signaling and IFN-inducible biological responses2012

    • Author(s)
      Sharma B, Joshi S, Sassano A, Majchrzak B, Kaur S, Aggarwal P, Nabet B, Bulic M, Stein BL, McMahon B, Baker DP, Fukunaga R, Altman JK, Licht JD, Fish EN, Platanias LC
    • Journal Title

      J Biol Chem

      Volume: 287(50) Pages: 42352-42360

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] EED mutants impair polycomb repressive complex 2 in myelodysplastic syndrome and related neoplasms2012

    • Author(s)
      Ueda T, Sanada M, Matsui H, Yamasaki N, Honda ZI, Shih LY, Mori H, Inaba T, Ogawa S, Honda H
    • Journal Title

      Leukemia

      Volume: 26(12) Pages: 2557-2560

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function2012

    • Author(s)
      Sasaki M, Knobbe CB, Itsumi M, Elia AJ, Harris IS, Chio II, Cairns RA, McCracken S, Wakeham A, Haight J, Ten AY, Snow B, Ueda T, Inoue S, Yamamoto K, Ko M, Rao A, Yen KE, Su SM, Mak TW
    • Journal Title

      Genes Dev

      Volume: 26(18) Pages: 2038-2049

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRADD contributes to tumour suppression by regulating ULF-dependent p19(Arf) ubiquitylation2012

    • Author(s)
      Chio II, Sasaki M, Ghazarian D, Moreno J, Done S, Ueda T, Inoue S, Chang YL, Chen NJ, Mak TW
    • Journal Title

      Nat Cell Biol

      Volume: 14(6) Pages: 625-633

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential role for Mnk kinases in type II interferon (IFN{gamma}) signaling and its suppressive effects on normal hematopoiesis2011

    • Author(s)
      Joshi S, Sharma B, Kaur S, Majchrzak B, Ueda T, Fukunaga R, Verma AK, Fish EN, Platanias LC
    • Journal Title

      J Biol Chem

      Volume: 286(8) Pages: 6017-6026

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 遺伝子改変マウスを用いた造血器腫瘍関連EED Ile363Met変異体の解析2013

    • Author(s)
      上田健, 真田昌, 松井啓隆, 山崎憲政, 本田善一郎, 森啓, LEE-YUNG SHIH, 稲葉俊哉, 小川誠司, 本田浩章
    • Organizer
      第75回日本血液学会
    • Place of Presentation
      札幌
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of interacting partners for MAP kinase-interacting kinase 12013

    • Author(s)
      上田健, 福永理己郎, Roumiana Alexandrova, Theo Goh, Tak W. Mak, 本田浩章
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-11
    • Related Report
      2013 Final Research Report
  • [Presentation] MDSで同定されたポリコーム複合体PRC2構成因子EEDの機能欠失型変異体の解析2012

    • Author(s)
      上田健, 真田昌, 松井啓隆, 山崎憲政, 本田善一郎, 森啓, LEE-YUNG SHIH, 稲葉俊哉, 小川誠司, 本田浩章
    • Organizer
      第74回日本血液学会
    • Place of Presentation
      京都
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 骨髄異形成症候群におけるポリコーム複合体PRC2構成因子EEDの機能欠失型変異2011

    • Author(s)
      上田健, 真田昌, 松井啓隆, 山崎憲政, 本田善一郎, 森啓, LEE-YUNG SHIH, 稲葉俊哉, 小川誠司, 本田浩章
    • Organizer
      第73回日本血液学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌の治療標的としてのMnk/eIF4E経路2011

    • Author(s)
      上田健
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌の治療標的としてのMnk/eIF4E経路2011

    • Author(s)
      上田 健
    • Organizer
      日本生化学会(招待講演)
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] Identification of interacting partners for MAP kinase-interacting kinase 1

    • Author(s)
      上田 健、福永理己郎、Roumiana Alexandrova、Theo Goh、Tak W. Mak、本田浩章
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report

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

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