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

2012 Fiscal Year Final Research Report

• 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
• Keywords: p53 / MDM4

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: Vol. 63 (No. 6) Pages: 91-100
  • DOI: DOI:pii:S0302-2838(12)01405-4.10.1016/j.eururo.2012.11.030
  • Peer Reviewed
• [Journal Article] DNA methyltransferase 1 is essetial for initiation of the colon cancers (2013)
  • Author(s): Morita R, Hirohashi Y, Suzuki H, Takahashi A, Tamura Y, Kamaseki T, Asanuma H, Inoda S, Kondo T, Hashino S, Hasegawa T, Tokino T, Toyota M, Asaka M, Torigoe T, Sato N
  • Journal Title: Exp Mol Pathol Volume: Vol. 94 (No. 2) Pages: 322-329
  • DOI: DOI:10.1016/j.yexmp.2012.10.004
  • 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)
  • DOI: 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 Biology Therapy Volume: Vol.13 (No. 14) Pages: 1512-1521
  • DOI: 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 Therapy Volume: Vol. 19 (No. 11) Pages: 749-756
  • DOI: DOI:10.1038/cgt.2012.51
  • Peer Reviewed
• [Journal Article] CHFR protein regulates mitotic checkpoint by targeting PARP-1 protein for ubiquitination and degradation (2012)
  • Author(s): Kashima L, Idogawa M, Mita H, Shitashige M, Yamada T, Ogi K, Suzuki H, Toyota M, Sasaki Y, *Tokino T
  • Journal Title: J Biol Chem Volume: Vol. 287 (No. 16) Pages: 12975-12984
  • DOI: 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): Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y
  • Journal Title: Cancer Research Volume: Vol. 72 (No. 5) Pages: 1126-1136
  • DOI: DOI:10.1158/0008-5472.CAN-11-1803
  • Peer Reviewed
• [Journal Article] Molecular dissection of premalignant colorectal lesions reveals early onset of CpG island methylator phenotype (2012)
  • Author(s): Yamamoto E, Suzuki H, Yamano HO, Maruyama R, Nojima M, Kamimae S, Sawada T, Ashida M, Yoshikawa K, Kimura T, Takagi R, Harada T, Suzuki R, Sato A, Kai M, Sasaki Y, Tokino T, Sugai T, Imai K, Shinomura Y, Toyota M
  • Journal Title: Am J Pathol Volume: Vol. 181 (No. 5) Pages: 1847-1861
  • DOI: 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, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Suzuki R, Yamamoto H, Kai M, Tokino T, Sugai T, Imai K, Toyota M, Shinomura Y
  • Journal Title: Cancer Prev Ther (Phila) Volume: Vol. 5 (No. 10) Pages: 1203-1212
  • DOI: DOI:10.1158/1940-6207.CAPR-12-0056
  • Peer Reviewed
• [Journal Article] Heat shock enhances the expression of cyctoxic 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: Vol.17 (No. 6) Pages: 757-763
  • DOI: 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: Tumor Biol Volume: 33(5) Pages: 1307-1317
  • DOI: DOI:10.1007/s13277-012-0378-3
  • Peer Reviewed
• [Journal Article] Negative regulation of hepatoma-derived growth factor by p53 (2011)
  • Author(s): Sasaki Y, Negishi H, Yokota I, Koyama R, Kusano M, Suzuki H, Fujita M, Maruyama R, Toyota M, Saito T, Tokino T
  • Journal Title: Cancer Res Volume: Vol. 71 (No. 22) Pages: 7038-7047
  • DOI: 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, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, Kai M, Yamano H, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M
  • Journal Title: Cancer Res Volume: Vol. 71 (No. 17) Pages: 5646-5658
  • DOI: DOI:10.1158/0008-5472.CAN-11-1076
  • Peer Reviewed
• [Journal Article] Cystein-rich intestinal protein 2 (CRIP2)acts as a repressor of NF-kB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis (2011)
  • Author(s): Cheung AK, Ko JM, Lung HL, Chan KW, Stanbridge EJ, Zabarovsky E, Tokino T, Kashima L, SuzukiT, Kwong DL, Chua D, Tsao SW, Lung ML
  • Journal Title: Pros Natl Acad Sci US Volume: Vol. 108 (No. 20) Pages: 8390-8395
  • DOI: 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): Kamimae S, Yamamoto E, Yamano HO, Nojima M, Suzuki H, Ashida M, Hatahira T, Sato A, Kimura T, Yoshikawa K, Harada T, Takamaru H, Maruyama R, Kai M, Nishikawa M, Sugai T, Sasaki Y, Tokino T, Shinomura Y, Imai K, *Toyota M
  • Journal Title: Cancer Prev Res(Phila) Volume: Vol. 4 (No. 5) Pages: 674-683
  • DOI: 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 Pages: 4867-4874
  • DOI: DOI:10.3748/wjg.v17.i44.4867
  • Peer Reviewed
• [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
  • Industrial Property Number: 2012-187062
  • Filing Date: 2012-08-27