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Redox regulation of inflammation and carcinogenesis mediated by NF-κB/IKKβ and dual-specificity phosphatase

Research Project

Project/Area Number 18570136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHiroshima University

Principal Investigator

KAMATA Hideaki  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (10233925)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,910,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsREDOX / CANCER / INFLAMMATION / IKKβ / OXIDATIVE STRES / NF-κB / MAP KINASE PHOSPHATASE / NF-kB / MAPキナーゼホスファターゼ
Research Abstract

A major link between inflammation and carcinogenesis depends on several cellular signaling systems including the ilacp/NF-кB pathway and the MAP kinase cascade. Especially, tumor necrosis factor (TNF・), which activates NF-кB through IKKβ and JNK, plays an important role both inflammation and carcinogenesis. To reveal how these signaling systems regulate inf lammation and carci nogenesis, we investigated cellular responses of mutant cells deficlent in NF-кB activation. TNF・induced reactive oxygen species (ROS) production in these mutant cells and lead cell death. TNF・-mediated cell death is thought to be profoundly involved in carcinogenesis in liver. Cell death is medicated by inactivation of several tyrosine phosphatases of which active site is redox-sensitive cysteine residue including MAP kinase phosphatases. Inactivation of MKPs leads the sustained JNK activation and caspase activation. Interestingly, although ROS oxidize PTEN, the down stream kinase Akt of which activation can promote cell survival is degraded by caspases. Thus, TNF・induces cell death by inactivation of MKP and by Akt degradation mediated by oxidative stress.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (33 results)

All 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 10 results) Presentation (11 results)

  • [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice.2008

    • Author(s)
      Yuko Koketsu, et. al
    • Journal Title

      Am J Physiol Endocrinol Metab. 294

      Pages: 719-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nu trients.2008

    • Author(s)
      Junko Fujio, et al.
    • Journal Title

      Diabetes Res Clin Pract. 79

      Pages: 2-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatic overexpression of a doninant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice.2008

    • Author(s)
      Yuko Koketsu, Hideyuki Sakoda, Midori Fujishiro, Akifurni Kushiyama, Yasushi Fukushima, Hiraku Ono, Motonobu Anai, Takako Kikuchi, Takeshi Fukuda, Hideaki Kamata, Nanao Hor ike, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
    • Journal Title

      Am J Physiol Endocrinol Metab. 294(4)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nutrients.2008

    • Author(s)
      Junko Fujio, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Takehide Ogihara, Yasushi Fukushima, Motonobu Anai, Nanao Hor ike, Hideaki Kamata, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
    • Journal Title

      Diabetes Res Clin Pract. 79

      Pages: 2-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice.2008

    • Author(s)
      Yuko Koketsu, et. al.
    • Journal Title

      Am J Physiol Endocrinol Metab. 294

      Pages: 719-25

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nutrients.2008

    • Author(s)
      Junko Fujio, et. al.
    • Journal Title

      Diabetes Res Clin Pract. 79

      Pages: 2-10

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carboxy1-terminal modulator protein (ctmp)induces akt phosphorylation and activation, thereby enhancing anti-apoptotic, glycogen synthetic and glucose uptake pathways.2007

    • Author(s)
      Hiraku Ono, et al.
    • Journal Title

      Am J Physiol Cell Physiol. 293

      Pages: 1576-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Suppression of AP-1 Activity by Cycloprodigiosin Hydrochloride.2007

    • Author(s)
      Keiko Kawauchi
    • Journal Title

      Biol. Pharm. Bull 30

      Pages: 1792-1795

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Role of Phosphatidylinositol 3-Kinase Activation on Insulin Action and Its Alteration in Diabetic Conditions.2007

    • Author(s)
      Tomoichiro Asano, et al.
    • Journal Title

      Biol. Pharm. Bull 30

      Pages: 1610-1616

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Carboxyl-terminal modulator protein (ctmp) induces akt phosphorylation and activation, thereby enhancing anti-apoptotic, glycogen synthetic and glucose uptake pathways.2007

    • Author(s)
      Hiraku Ono, Hideyuki Sakoda, Midori Fujishiro, Motonobu Anai, Akifumi Kushiyama, Yasushi Fukushima, Hideki Katagiri, Takehide Ogihara, Yoshitomo Oka, Hideaki Kamata, Nanao Horike, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
    • Journal Title

      Am J Physiol Cell Physiol. 293(5)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Suppression of AP-1 Activity by Cycloprodigiosin Hydrochloride.2007

    • Author(s)
      Keiko Kawauchi, Kei Tobiume, Shuhei Kaneko, Keiko Kaneshiro, Shiho Okamoto, Emi Ueda, Hideaki Kamata, Yoshinori Moriyama, Hajime Hirata
    • Journal Title

      Biol. Pharm. Bull. 30(9)

      Pages: 1792-1795

    • NAID

      110006380271

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of Phosphatidylinositol 3-Kinase Activation on Insulin Action and Its Alteration in Diabetic Conditions.2007

    • Author(s)
      Tomoichiro Asano, Midori Fujishiro, Akifumi Kushiyama, Yusuke Nakatsu, Masayasu Yoneda, Hideaki Kamata, Hideyuki Sakoda
    • Journal Title

      Biol. Pharm. Bull. 30(9)

      Pages: 1610-1616

    • NAID

      110006380237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Carboxyl-terminal modulator protein (ctmp) induces akt phosphorylation and activation, thereby enhancing anti-apoptotic, glycogen synthetic and glucose uptake pathways.2007

    • Author(s)
      Hiraku Ono, et. al.
    • Journal Title

      Am J Physiol Cell Physiol. 293

      Pages: 1576-85

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Phosphatidylinositol 3-Kinase Activation on Insulin Action and Its Alteration in Diabetic Conditions.2007

    • Author(s)
      Tomoichiro Asano, et. al.
    • Journal Title

      Biol. Pharm. Bull 30

      Pages: 1610-1616

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The E3 ubiquitin ligase Itch couples JNK aotivation to TNF-induced cell death by inducing c-FLIPL turnover2006

    • Author(s)
      Lufen Chang, et al
    • Journal Title

      Cell 124

      Pages: 601-613

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 活性線素によるチロシンホスフアターゼの調節2006

    • Author(s)
      鎌田英明
    • Journal Title

      分子細胞治療 5

      Pages: 28-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] インスリンシグナルと2型糖尿病2006

    • Author(s)
      浅野知一郎, 鎌田英明
    • Journal Title

      遺伝子医学MOOK 6

      Pages: 255-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
  • [Journal Article] 血糖調節における視床下部ピルビン酸代謝の役割2006

    • Author(s)
      米田真康, 鎌田英明, 浅野知一郎
    • Journal Title

      Annual Review 糖尿病・代謝・内分泌

      Pages: 20-23

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
  • [Journal Article] The E3 ubiquitin I igase Itch couples JNK activation to TNF-induced cell death by inducing c-FLIPL turnover.2006

    • Author(s)
      Lufen Chang, Hideaki Kamata, Giovanni Solinas, Jun-Li Luo, Shin Maeda, K Venuprasad, Yun-Cai Liu, Michael Karin.
    • Journal Title

      Cell. 124

      Pages: 601-613

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Physiological significance of resistin and resistin-like molecules in the inflammatory process and insulin resistance.2006

    • Author(s)
      Tomoichiro Asano, Hideyuki Sakoda, Midori Fujishiro, Motonobu Anai, Akifumi Kushiyama, Nanako Horike, Hideaki Kamara, Hiroki Kurihara, Yasunobu Uchijima
    • Journal Title

      Current Diabetes Reviews 2

      Pages: 449-454

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The E3 ubiquitin ligase Itch couples JNK activation to TNF-induced cell death by inducing c-FLIPL turnover2006

    • Author(s)
      Lufen Chang et al.
    • Journal Title

      Cell 124

      Pages: 601-613

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 活性線素によるチロシンホスファターゼの調節2006

    • Author(s)
      鎌田英明
    • Journal Title

      分子細胞治療 5

      Pages: 28-34

    • Related Report
      2006 Annual Research Report
  • [Presentation] TNFαによるIKK非依存的IκBαの分解制御に関する機能解析2007

    • Author(s)
      土谷佳弘, 夏原芳里, 浅野知一郎, 鎌田英明
    • Organizer
      第30回日本分子生物学会・第80回日本生化学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 酸化ストレスに応答して誘導されるIKKγ/NEMOの分子間ジスルフィド結合2007

    • Author(s)
      夏原芳里, 土谷佳弘, 浅野知一郎, 鎌田英明
    • Organizer
      第30回日本分子生物学会・第80回日本生化学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 高脂肪食によるLKBl-AMPK・SIK-T0RC2 pathway障害の分子機構2007

    • Author(s)
      米田真康, 大野晴也, 迫田秀之, 中津祐介, 崔 興龍, 張 君, 郭 螢, 江川 真希子, 鎌田英明, 浅野 知一郎
    • Organizer
      第19回分子糖尿病学シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of IKK-independent degradation of I・B・ by TNF・.2007

    • Author(s)
      Yoshihiro Tsuchiya, Kaori Natsuhara, Tomoichiro Asano, Hideaki Kamata
    • Organizer
      Annual Meeting of Japanese Biochemical Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Oxidative stress forms disulfide bonds of IKK・/NEM0.2007

    • Author(s)
      Kaori Natsuhara, Yoshihiro Tsuchiya, Tomoichiro Asano, Hideaki Kamata
    • Organizer
      Annual Meeting of Japanese Biochemical Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular mechanism of failure in LKB1-AMPK・SIK-TORC2 pathway by high-fat diet.2007

    • Author(s)
      Masayasu Yoneda, Haruya Ono, Hideayuki Sakoda, Yusuke Nakatsu, Kouryu Sak Kun Cyou, Ei Kaku, Makiko Egawa, Hideaki Kamata, Tomoichiro Asano
    • Organizer
      Symposium of molecular diabetes.
    • Place of Presentation
      Kobe
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 高脂肪食によるLKB1-AMPK・SIK-TORC2 pathway障害の分子機構2007

    • Author(s)
      米田真康、大野晴也、迫田秀之、中津祐介、崔 興龍、張 君、郭 瑩、江川 真希子、鎌田英明、浅野 知一郎
    • Organizer
      第19回分子糖尿病学シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] MAPキナーゼホスフアターゼ(MKPs)とPTENを介した細胞の生と死のレドツクス制御2007

    • Author(s)
      鎌田英明
    • Organizer
      レドックス生命科学研究会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Redox regulation of cell life and death by MAP kinase phosphatase and PTEN.2007

    • Author(s)
      Hideaki Kamata
    • Organizer
      Redox life science meeting.
    • Place of Presentation
      Osaka
    • Year and Date
      2007-03-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] MAPキナーゼホスフアクーゼ(MKPs)とPTENの共役による細胞死と細胞増殖のレドツクス制御2006

    • Author(s)
      鎌田英明 土谷佳弘, 夏原芳里, 平田肇, 浅野知一郎
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Redox regulation of cell death and proliferation by coupling of MAP kinase phosphatase (MKP) and PTEN.2006

    • Author(s)
      Hideaki Kamata. Yoshihiro Tsuchiy, Kaori Natsuhar, Hajime Hirata, Tomoichiro Asano
    • Organizer
      Annual Meeting of Japanese Cancer Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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