1995 Fiscal Year Final Research Report Summary
Molecular cloning of cDNAs for transcriptional factors of indoleamine 2,3-dioxygenase induced by IFN-gamma
| Project/Area Number |
06680636
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
TAKIKAWA Osamu Osaka Bioscience Institute, Department of Cell Biology, Research Scientist, 第4研究部・研究所, 研究員 (70163342)
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| Co-Investigator(Kenkyū-buntansha) |
TONE Shigenobu The Tokyo Metropolitan Institute for Medical Science Department of Radiation Bio, 放射線医学部門・総合研究所, 研究員 (70211399)
YOSHIDA Ryotaro Osaka Bioscience Institute, Department of Cell Biology, Head, 第4研究部・研究所, 部長 (10124760)
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| Project Period (FY) |
1994 – 1995
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| Keywords | STAT 1 / interferon-gamma / indoleamine 2,3-dioxygenase / transcriptional factor / IRF-1 / tryptophan metabolism / cytokine / ISRE |
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| Research Abstract |
The purpose of this study is to characterize the transcriptional factors involved in the IFN-gamma-mediated induction of indoleamine 2,3-dioxygenase (IDO), a tryptophan degrading enzyme. Until 1994, we have demonstrated that two IDO mRNAs, 1.7kb and 2.3kb, whch differ in size of 5' franking region are induced by IFN-gamma in all human cultured cell lines examined. Kinetics of both mRNA induction and analyzes of the 5' control region of IDO gene expression have shown that 1) induction of both mRNAs are blocked by inhibitors for protein synthesis, indicating the need for a de novo synthesis of protein factor (s), 2) the protein synthesis occurs within 3 h after the addition of IFN-gamma, 3) the 5' region of 1.7kb mRNA that contains IRF-1 element, ISRE element, a Y-box, and a X-box but has no IFN-gamma-responsive promoting activity for transcription of IDO mRNA,and 4) the 5' region of 2.3kb mRNA has an ISRE and a X-box with the IFN-gamma responsive enhancing activity.
In 1995, we have examined the presence of regulatory protein (s) for the enhance element for transcription of 2.3kb IDO mRNA in nuclear or cytoplasmic extract of human lung fibroblasts (HEL), which exhibited the highest induction of IDO by the addition of IFN-gamma. However, we have not yet detect such factor (s) in the nuclear extract. On the other hand, Gupta et al [J Interferon Res.15 : 517-526 (1995)] have reported that both STAT1 and IRF-1 are involved in the transcription of IDO mRNA.To confirm this, analysis of IDO induction by IFN-gamma in STAT1 and IRF-1 deficient mice is in progress.
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