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High-throughput screening for peptides that inhibit the interaction or MDM4 with p53

Research Project

Project/Area Number 23659658
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionSapporo Medical University

Principal Investigator

TOKINO Takashi  札幌医科大学, 医学部, 教授 (40202197)

Co-Investigator(Kenkyū-buntansha) FURUHATA Tomohisa  札幌医科大学, 医学部, 准教授 (80359992)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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)
Keywordsp53 / MDM4 / 癌 / 分子標的
Research Abstract

It is currently of great midical interest to inhibit specific protein-protein interactions between MDM4 and p53. Here, we developed a method using T7 phage display to screen for candidate inhibitors of MDM4-p53 interactions. In primary screening , we identified novel peptide motifs that inhibit the interaction of MDM4 with p53. Then, we designed a number of peptides that are predicted to have higher affinity to MDM4, and identified potential peptides that inhibit the interaction between MDM4 and p53 with higher affinity.

Report

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

    (30 results)

All 2013 2012 2011 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (5 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer2013

    • Author(s)
      Shimizu T, Suzuki H, Nojima M, Kitamura H, Yamamoto E, Maruyama R, Ashida M, Hatahira T, Kai M, Masumori N, Tokino T, Imai K, Tsukamoto T, Toyota M
    • Journal Title

      Eur Urol

      Volume: 63 Issue: 6 Pages: 1091-1100

    • DOI

      10.1016/j.eururo.2012.11.030

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA methyltransferase 1 is essential for initiation of the colon cancers2013

    • Author(s)
      Morita R,Hirohashi Y,Suzuki H, et al
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 94 Issue: 2 Pages: 322-329

    • DOI

      10.1016/j.yexmp.2012.10.004

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer.2013

    • Author(s)
      Shimizu T et al
    • Journal Title

      Eur Urol

      Volume: VOL. 63 Pages: 1091-1100

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic vulnerability to LINE-1 hypermethylation is a potential determinant of the clinicogenetic features of multiple myeloma.2012

    • Author(s)
      Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, Itagaki M, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y
    • Journal Title

      Genome Medicine

      Volume: (印刷中) Issue: 12

    • DOI

      10.1186/gm402

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion2012

    • Author(s)
      Sasaki Y, Sugisaka J, Maruyama R, Sugisaka J, Tamura M, Sugisaka J, Suzuki H, Idogawa M, Shinomura Y, Tokino T
    • Journal Title

      Cancer Biol Ther

      Volume: 13 Issue: 14 Pages: 1512-1521

    • DOI

      10.4161/cbt.22280

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel approach to cancer treatment using structural hybrids of the p53 gene family.2012

    • Author(s)
      Sasaki Y, Oshima Y, Koyama R, Tamura M, Kashima L, Idogawa M, Yamashita T, Toyota M, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      Cancer Gene Ther

      Volume: 19 Issue: 11 Pages: 749-56

    • DOI

      10.1038/cgt.2012.51

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation2012

    • Author(s)
      Kashima, L., Idogawa, M., Mita, H., Shitashige, M., Yamada, T., Ogi, K., Suzuki, H., Toyota, M., Ariga, H., Sasaki, Y., Tokino, T.
    • Journal Title

      J. Biol. Chem

      Volume: 287 Issue: 16 Pages: 12975-12984

    • DOI

      10.1074/jbc.m111.321828

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors2012

    • Author(s)
      Takeshi Niinuma
    • Journal Title

      Cancer research

      Volume: 72 Issue: 5 Pages: 1126-36

    • DOI

      10.1158/0008-5472.can-11-1803

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Dissection of Premalignant Colorectal Lesions Reveals Early Onset of the CpG Island Methylator Phenotype.2012

    • Author(s)
      Yamamoto E, Suzuki H, Yamano HO
    • Journal Title

      Am J Pathol

      Volume: 181(5) Issue: 5 Pages: 1847-61

    • DOI

      10.1016/j.ajpath.2012.08.007

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer.2012

    • Author(s)
      Takamaru H, Yamamoto E, Suzuki H.
    • Journal Title

      Cancer Prev Res (Phila)

      Volume: 5(10) Issue: 10 Pages: 2012-2012

    • DOI

      10.1158/1940-6207.capr-12-0056

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes2012

    • Author(s)
      Takahashi A, Torigoe T, Tamura Y, Kanaseki T, Tsukahara T, Sasaki Y, Kameshima H, Tsuruma T, Hirata K, Tokino T, Hirohashi Y, Sato N
    • Journal Title

      Cell Stress Chaperones

      Volume: 17 Issue: 6 Pages: 757-763

    • DOI

      10.1007/s12192-012-0348-0

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma2012

    • Author(s)
      Shitani M, Sasaki S, Akutsu N, Takagi H, Suzuki H, Nojima M, Yamamoto H, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y
    • Journal Title

      Tumour Biol

      Volume: 33 Issue: 5 Pages: 1307-1317

    • DOI

      10.1007/s13277-012-0378-3

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation2012

    • Author(s)
      Kashima L et al
    • Journal Title

      J Biol Chem

      Volume: VOL. 287

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors2012

    • Author(s)
      Niinuma T et al
    • Journal Title

      Cancer Research

      Volume: VOL. 72 Pages: 1126-1136

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] p53 negatively regulates the hepatoma growth factor HDGF2011

    • Author(s)
      Sasaki Y, Negishi H, Idogawa M, Yokota I, Koyama R, Kusano M, Suzuki H, Fujita M, Maruyama R, Toyota M, Saito T, Tokino T
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 22 Pages: 7038-47

    • DOI

      10.1158/0008-5472.can-11-1053

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer2011

    • Author(s)
      Suzuki H
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 17 Pages: 5646-5658

    • DOI

      10.1158/0008-5472.can-11-1076

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cystein-rich intestinal protein 2 (CRIP2) acts as a repressor of NFkB-mediated pro-angiogenic cytokins transcription to suppress tumorigenesis and angiogenesis2011

    • Author(s)
      Cheung, K.L., 7名略, Suzuki, T., 4名略
    • Journal Title

      Proceeding of National Academy of Science USA

      Volume: 108 Issue: 20 Pages: 8390-8395

    • DOI

      10.1073/pnas.1101747108

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors2011

    • Author(s)
      Seiko Kamimae
    • Journal Title

      Cancer prevention research

      Volume: 4 Issue: 5 Pages: 674-83

    • DOI

      10.1158/1940-6207.capr-10-0214

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer.2011

    • Author(s)
      Tayama M, Furuhata T, Inafuku Y, Okita K, Nishidate T, Mizuguchi T, Kimura Y, Hirata K
    • Journal Title

      World J Gastroenterol

      Volume: 17 Issue: 44 Pages: 4867-4874

    • DOI

      10.3748/wjg.v17.i44.4867

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] p53 negatively regulates the hepatoma growth factor HDGF2011

    • Author(s)
      Sasaki Y et al
    • Journal Title

      Cancer Research

      Volume: VOL. 71 Pages: 7038-7047

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cysteine-rich intestinal protein 2 (CRIP2) acts as a repressor of NF-kappaB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis2011

    • Author(s)
      Cheung AK et al
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: VOL. 108 Pages: 8390-8395

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer2011

    • Author(s)
      Suzuki H et al
    • Journal Title

      Cancer Research

      Volume: VOL. 71 Pages: 5646-5658

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] p53研究の新展開2012

    • Author(s)
      時野 隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of novel p53 target genes by ChIP-Seq and mRNA expression analysis combined with genome-wide p53-binding motif analysis in silico.2011

    • Author(s)
      Idogawa M, (Tokino T)
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-04-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Apoptosis induction in cancer cells by the simultaneous transduction of p53 and artificial miRNAs based on the screening of genome-wide shRNA library2011

    • Author(s)
      Idogawa M, (Tokino T)
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-04-03
    • Related Report
      2012 Final Research Report
  • [Presentation] The functional relationship between CHFR and PARP-1 controls the antephase checkpoint and tumor development2011

    • Author(s)
      Kashima L, (Tokino T)
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-04-03
    • Related Report
      2012 Final Research Report
  • [Presentation] A comprehensive analysis to screen for epigenetically silenced miRNA genes in colorectal cancer2011

    • Author(s)
      Suzuki H, (Tokino T)
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-04-03
    • Related Report
      2012 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://web.sapmed.ac.jp/canmol/

    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] p53キメラ遺伝子を含む抗腫〓剤2012

    • Inventor(s)
      時野隆至、佐々木泰史、井戸川雅史
    • Industrial Property Rights Holder
      札幌医科大学
    • Filing Date
      2012-08-27
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] p53キメラ遺伝子を含む抗腫瘍剤2012

    • Inventor(s)
      時野 隆至
    • Industrial Property Rights Holder
      札幌医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-187062
    • Filing Date
      2012-08-27
    • Related Report
      2012 Annual Research Report

URL: 

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

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