| Project/Area Number |
10044331
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
KOHNO Kimitoshi Univ. of Occcup. & Envir. Health School of Medicine, Professor, 医学部, 教授 (00153479)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMI Hiroto Univ. of Occcup. & Envir. Health School of Medicine, Professor, 医学部, 助手 (50289576)
NOMOTO Minoru Univ. of Occcup. & Envir. Health School of Medicine, Assistant Professor, 医学部, 講師 (00164749)
FUNA Keiko ゲーテブルグ大学, 医学部, 教授
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | MDR1 / CCAAT / YB-1 / p53 / NF-Y / c-Myc / HMG1 / CTF / NF1 / c-myc / PCNA |
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| Research Abstract |
From a point of view of drug resistance, we focused on the MDR1 gene expression and, investigated its regulatory mechanism. Promoter region in MDR1 gene has a CCAAT motif, and YB-1 and NF-Y can bind to this motif. The trial of identification of the interacting molecules bound to YB-1 and NF-Y were carried out in Japan and Sweden, respectively. So far, we found that p53 (tumor suppresser gene) interacted YB-1. Then the interaction domain between p53 and YB-1, and the mechanism of MDR1 gene expression by p53 through interaction with YB-1 were investigated in Japan. In Sweden, Prof. Funa identified the c-Myc as a factor which interacted with NF-Y, and investigated the interaction domain of each protein and the effect of mutual interaction on transcriptional regulation of down-stream genes. She also found that p53 binds to NF-Y. She is going to investigate the interaction domain. On the other hand, expression mechanism of the HMG1 and STAT3 genes as genes induced by DNA damage were identified in Japan. It was suggested that HMG1 gene expression was regulated by a transcription factor CTF/NF1 through the binding to the promoter region of HMG1. Furthermore, HMG1 interacted p53, and recognized the cisplatin-damaged DNA, and this recognition activity was enhanced by p53. We also found that STAT3 gene expression was upregulated in cisplatin-resistant cells through alternation of chromatin structure. Prof. Funa and I are going to identify the promising molecules for gene therapy, such as damaged DNA recognition protein, cell-cycle. regulatory protein and DNA repair protein and to construct the molecular interaction map for controlling cancer cell growth.
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