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Enhancement of drug-sensitivity through the reactivation of mutant p53

Research Project

Project/Area Number 23501278
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

OZAKI TOSHINORI  千葉県がんセンター(研究所), その他部局等, 研究員 (40260252)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがん抑制遺伝子
Research Abstract

We have identified co-chaperon human DnaJC7 as one of the binding partners of mutant p53. According to our immunoprecipitation experiments, DnaJC7 was associated with mutant p53 as well as wild-type p53 in mammalian cultured cells. Of note, DnaJC7 promoted the dissociation of MDM2 from wild-type p53, and thereby extended its half-life and stimulated its transcriptional as well as pro-apoptotic activity. In addition, luciferase reporter assays demonstrated that DnaJC7 has an ability to reduce the inhibitory effect of mutant p53 on wild-type p53. Taken together, our present results strongly suggest that DnaJC7 might enhance the drug-sensitivity of malignant cancerous cells through the physical and functional interactions with wild-type p53 and/or mutant p53.

Report

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

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results,  Open Access: 1 results) Presentation (8 results)

  • [Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer Pyrrole-Imidazole polyamide targeting E-box2014

    • Author(s)
      Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Kojima T, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma M, and Nagase H
    • Journal Title

      FEBS Open Bio

      Volume: 4 Pages: 328-334

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Receptor-type protein tyrosine phosphatase к (PTPRK) directly dephosphorylates CD133 and regulates downstream AKT activation2014

    • Author(s)
      Shimozato O, Waraya M, Nakashima K, Soda H, Takiguchi N, Yamamoto H, Takenobu H, Uehara H, Ikeda E, Matsushita S, Kubo N, Nakagawara A, Ozaki T, Kamijo T
    • Journal Title

      Oncogene

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets E-box.2014

    • Author(s)
      134. Taniguchi M, Nakai Y, Ozaki T, Koshikawa N, Kojima T, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma T, Nagase H.
    • Journal Title

      FEBS Open Bio

      Volume: 4 Issue: 1 Pages: 328-334

    • DOI

      10.1016/j.fob.2014.03.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Receptor-type protein tyrosine phosphatase κ (PTPRK) directly dephosphorylates CD133 and regulates downstream AKT activation.2014

    • Author(s)
      Shimozato O, Waraya M, Nakashima K, Soda H, Takiguchi N, Yamamoto H, Takenobu H, Uehara H, Ikeda E, Matsushita S, Kubo N, Nakagawara A, Ozaki T, Kamijo T.
    • Journal Title

      Oncogene

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Co-chaperon DnaJC7/TPR2 enhances p53 stability and activity through blocking the complex formation between p53 and MDM22013

    • Author(s)
      Kubo N, Wu D, Yoshihara Y, Sang M, Nakagawara A, Ozaki T
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Pages: 1034-1039

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Runt-related transcription factor 2 (RUNX2) inhibits p53-dependent apoptosis through the collaboration with HDAC6 in response to DNA damage2013

    • Author(s)
      Ozaki T,Wu D, Sugimoto H, Nagase H, Nakagawara A
    • Journal Title

      Cell Death Dis.

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression2013

    • Author(s)
      Zhu Y, Li Y, Haraguchi S, Yu M, Ohira M, Ozaki T, Nakagawara A, Ushijima T, Isogai E, Koseki H, Nakamura Y, Kong C, Mehlen P, Arakawa H, Nakagawara A
    • Journal Title

      J. Clin. Invest.

      Volume: 123 Pages: 2935-2947

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint2013

    • Author(s)
      Ando K, Ozaki T, Hirota T, Nakagawara A
    • Journal Title

      PLoS One

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Co-chaperon DnaJC7/TPR2 enhances p53 stability and activity through blocking the complex formation between p53 and MDM2.2013

    • Author(s)
      Kubo N, Wu D, Yoshihara Y, Sang M, Nakagawara A, Ozaki T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Issue: 3 Pages: 1034-1039

    • DOI

      10.1016/j.bbrc.2012.11.121

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Runt-related transcription factor 2 (RUNX2) inhibits p53- dependent apoptosis through the collaboration with HDAC6 in response to DNA damage.2013

    • Author(s)
      Ozaki T, Wu D, Sugimoto H, Nagase H, Nakagawara A.
    • Journal Title

      Cell Death Dis.

      Volume: e610 Issue: 4 Pages: e610-e610

    • DOI

      10.1038/cddis.2013.127

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression.2013

    • Author(s)
      Zhu Y, Li Y, Haraguchi S, Yu M, Ohira M, Ozaki T, Nakagawa A, Ushijima T, Isogai E, Koseki H, Nakamura Y, Kong C, Mehlen P, Arakawa H, Nakagawara A.
    • Journal Title

      J Clin Invest.

      Volume: 123 Issue: 7 Pages: 2935-47

    • DOI

      10.1172/jci65988

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.2013

    • Author(s)
      Ando K, Ozaki T, Hirota T, Nakagawara A.
    • Journal Title

      PLoS One

      Volume: e82744 Issue: 12 Pages: 0-0

    • DOI

      10.1371/journal.pone.0082744

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Runt-related transcription factor 1 (RUNX1) stimulates tumor suppressor p53 in response to DNA damage through complex formation and acetylation.2013

    • Author(s)
      Wu D, Ozaki T, Yoshihara Y, Kubo N, Nakagawara A.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 1353-1364

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Co-chaperon DnaJC7/TPR2 enhances p53 stability and activity through blocking the complex formation between p53 and MDM2.2013

    • Author(s)
      Kubo N, Wu D, Yoshihara Y, Sang M, Nakagawara A, Ozaki T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Pages: 1034-1039

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Runt-related transcription factor 2 (RUNX2) inhibits p53- dependent apoptosis through the collaboration with HDAC6 in response to DNA damage.2013

    • Author(s)
      Ozaki T, Wu D, Sugimoto H, Nagase H, Nakagawara A.
    • Journal Title

      Cell Death Disease

      Volume: 未定

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] p53 依存性のDNA 損傷応答機構における RUNX2 の新たな役割2013

    • Author(s)
      尾崎俊文、永瀬浩喜、中川原章
    • Journal Title

      生化学

      Volume: 未定

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory role of E2F-1 in the regulation of tumor suppressor p53 during DNA damage response2012

    • Author(s)
      Yoshihara Y, Wu D, Kubo N, Sang M, Nakagawara A, Ozaki T
    • Journal Title

      Biochem, Biophys, Res. Commun.

      Volume: 421 Pages: 57-63

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] CREB represses p53-dependent transactivation of MDM2 through the complex formation with p53 and contributes to p53-mediated apoptosis in response to glucose deprivation2011

    • Author(s)
      Okoshi R, Kubo N, Nakashima K, Shimozato O, Nakagawara A, Ozaki T
    • Journal Title

      Biochem, Biophys, Res. Commun.

      Volume: 406 Pages: 79-84

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of p53 in cell death and human cancers2011

    • Author(s)
      Ozaki T, Nakagawara A
    • Journal Title

      Cancers

      Volume: 3 Pages: 994-1013

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA損傷刺激に応答したp53の活性化機構におけるRUNX3の新たな役割とアポトーシス誘導2011

    • Author(s)
      尾崎俊文、山田千寿、中川原章
    • Journal Title

      生化学

      Volume: 83 Pages: 751-754

    • NAID

      10029575150

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] RUNX2 inhibits p53-dependent apoptosis following DNA damage in collaboration with HDAC62013

    • Author(s)
      Ozaki T, Sugimoto H, Nakagawara A, Nagase H
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphorylation of NFBD1/MDC1 by plk1 regulates decatenation checkpoint-mediated G2/M transition2013

    • Author(s)
      Ando K, Ozaki T, Hirota T, Nakagawara A
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA 損傷に応答したアポトーシス誘導過程における複合体形成を介した RUNX1 による p53 の制御機構の解析2012

    • Author(s)
      呉丹、久保奈津美、尾崎俊文、中川原章
    • Organizer
      第 71 回日本癌学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] DNA 損傷応答過程におけるp53 と RUNX2 との機能的相互作用の解析2012

    • Author(s)
      尾崎俊文 呉丹、久保奈津美、上條岳彦、中川原章
    • Organizer
      第 71 回日本癌学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] DNA損傷に応答したRUNX1によるp53の活性化機構の解析2011

    • Author(s)
      呉丹、久保奈津美、吉原由佳里、尾崎俊文、中川原章
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] p53依存性アポトーシス誘導過程におけるRUNX2の役割2011

    • Author(s)
      久保奈津美、呉丹、中川原章、上條岳彦、尾崎俊文
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] RUNX2 inhibits p53-dependent apoptosis following DNA damage in collaboration with HDAC6

    • Author(s)
      Ozaki T, Sugimoto H, Nakagawara A, Nagase H.
    • Organizer
      日本癌学会
    • Place of Presentation
      YOKOHAMA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Phosphorylation of NFBD1/MDC1 by plk1 regulates decatenation checkpoint-mediated G2/M transition

    • Author(s)
      Ando K, Ozaki T, Hirota T, Nakagawara A.
    • Organizer
      日本癌学会
    • Place of Presentation
      YOKOHAMA
    • Related Report
      2013 Annual Research Report

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

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