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

• Project/Area Number: 23659658
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Sapporo 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: ¥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)
• Keywords: p53 / 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.

Research Products

• [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer (2013)
  • 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
  • Peer Reviewed
• [Journal Article] DNA methyltransferase 1 is essential for initiation of the colon cancers (2013)
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion (2012)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors (2012)
  • Author(s): Takeshi Niinuma
  • Journal Title: Cancer research Volume: 72 Issue: 5 Pages: 1126-36
  • DOI: 10.1158/0008-5472.can-11-1803
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma (2012)
  • 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
  • Peer Reviewed
• [Journal Article] CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation (2012)
  • Author(s): Kashima L et al
  • Journal Title: J Biol Chem Volume: VOL. 287
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors (2012)
  • Author(s): Niinuma T et al
  • Journal Title: Cancer Research Volume: VOL. 72 Pages: 1126-1136
  • Peer Reviewed
• [Journal Article] p53 negatively regulates the hepatoma growth factor HDGF (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer (2011)
  • Author(s): Suzuki H
  • Journal Title: Cancer Res Volume: 71 Issue: 17 Pages: 5646-5658
  • DOI: 10.1158/0008-5472.can-11-1076
  • 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 angiogenesis (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors (2011)
  • Author(s): Seiko Kamimae
  • Journal Title: Cancer prevention research Volume: 4 Issue: 5 Pages: 674-83
  • DOI: 10.1158/1940-6207.capr-10-0214
  • 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
  • Peer Reviewed
• [Journal Article] p53 negatively regulates the hepatoma growth factor HDGF (2011)
  • Author(s): Sasaki Y et al
  • Journal Title: Cancer Research Volume: VOL. 71 Pages: 7038-7047
  • 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 angiogenesis (2011)
  • Author(s): Cheung AK et al
  • Journal Title: Proc Natl Acad Sci USA Volume: VOL. 108 Pages: 8390-8395
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer (2011)
  • Author(s): Suzuki H et al
  • Journal Title: Cancer Research Volume: VOL. 71 Pages: 5646-5658
  • 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）
• [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
• [Presentation] Apoptosis induction in cancer cells by the simultaneous transduction of p53 and artificial miRNAs based on the screening of genome-wide shRNA library (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
• [Presentation] The functional relationship between CHFR and PARP-1 controls the antephase checkpoint and tumor development (2011)
  • 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
• [Presentation] A comprehensive analysis to screen for epigenetically silenced miRNA genes in colorectal cancer (2011)
  • 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
• [Remarks] ホームページ
  • URL: http://web.sapmed.ac.jp/canmol/
• [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
• [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