Development of a novel molecular target drug for cancer therapy.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14407
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: NOJIMA HIROSHI 大阪大学, 微生物病研究所, 教授 (30156195)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: サイクリンG1 / PP2A-B’γ / アポトーシス / 骨肉腫細胞 / 前立腺癌細胞 / 正常細胞 / ペプチド / 分子標的薬

Outline of Final Research Achievements

Here, we found that ELAS1, a twentynine amino acid peptide corresponding to the association domain of Cyclin G1 with protein phosphatase 2A, interacts with the B' gamma subunit of PP2A and competitively inhibits the association with Cyclin G1. We showed that ELAS1 induced apoptotic cell death in U2OS, a human osteosarcoma cells through prevention of dephosphorylation at Mdm2 pT218 and p53 pS46, following DNA double-strand break insults such as gamma-irradiation and irinotecan treatment. We also show that ELAS1 caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells, but not in normal KD cells. The adenovirus that express ELAS1 also killed SAS cells. Notably, Cy5 tagged ELAS1t, which contained only ten amino acids, also efficiently induced apoptosis in both DU145 and SAS cells, suggesting the usefulness of ELAS1t itself as a peptide. Taken together, our results suggest that ELAS1 is therapeutically useful as a peptide drug.

Free Research Field

分子細胞生物学