Enhancement of drug-sensitivity through the reactivation of mutant p53

2013 Fiscal Year Final Research Report

• Project/Area Number: 23501278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Chiba 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
• 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.

Research Products

• [Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer Pyrrole-Imidazole polyamide targeting E-box (2014)
  • 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
  • Peer Reviewed
• [Journal Article] Receptor-type protein tyrosine phosphatase к (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: (in press)
  • 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
  • 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. Pages: e610
  • 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, 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
  • 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 Pages: e82744
  • Peer Reviewed
• [Presentation] RUNX2 inhibits p53-dependent apoptosis following DNA damage in collaboration with HDAC6 (2013)
  • 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
• [Presentation] Phosphorylation of NFBD1/MDC1 by plk1 regulates decatenation checkpoint-mediated G2/M transition (2013)
  • 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