Molecular cloning of trans-acting factor cDNA for IFN-gamma-inducible indoleamine 2,3-dioxygenase

IFN-γ诱导吲哚胺 2,3-双加氧酶反式作用因子 cDNA 的分子克隆

• 批准号: 04680203
• 负责人: TAKIKAWA Osamu
• 金额: $ 1.34万
• 依托单位: Osaka Bioscience Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04680203/
• 关键词: Oxygenase; Interferon-gamma; Trans-acting factor; Signal transduction; Cytokine; Tryptophan metabolism; インターフェロン-γ; インターフェロンーγ; 誘導酵素; 分子生物学; 細胞内情報伝達

Until 1992, we have isolated the gene of indoleamine 2,3-dioxygenase (IDO), an IFN-gamma-inducible tryptophan degrading enzyme, from human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The 5' flanking region contains IFN-stimulated response element (ISRE) and X-box like sequences. These sequences have a promoting activity for transcription of IDO mRNA.The IFN-gamma-mediated production of the IDO mRNA was suppressed by protein synthesis inhibitors, indicating an involvement of protein(s) newly synthesized in the induction of mRNA.The synthesis of the protein(s) occurred within 3h after the addition of IFN-gamma.In 1993, we have examined the presence of trans-acting protein(s) for the enhancer element (ISRE and X-box) for transcription of 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. On the other hand, the expression of IDO gene was inhibited strongly by herbimycin A, an inhibitor for tyrosine kinase, suggesting an implication of a tyrosine kinase in the enzyme induction. Northern blotting analysis indicated that the human IDO gene is expressed abundantly in the thymus in addition to the placenta, lung, and small intestine.

直到1992年，我们以IDO cDNA为探针，从人类基因组DNA文库中分离出了吲哚胺2,3-双加氧酶（IDO）基因，这是一种IFN-γ诱导的色氨酸降解酶，并确定了其限制性图谱和部分核苷酸序列。 5' 侧翼区域包含 IFN 刺激反应元件 (ISRE) 和 X-box 样序列。这些序列对 IDO mRNA 的转录具有促进活性。IFN-γ 介导的 IDO mRNA 产生被蛋白质合成抑制剂抑制，表明新合成的蛋白质参与了 mRNA 的诱导。蛋白质的合成发生在添加 IFN-γ 后 3 小时内。1993 年，我们检查了反式作用的存在 增强子元件（ISRE 和 X-box）的蛋白质，用于在人肺成纤维细胞 (HEL) 的核或细胞质提取物中转录 IDO mRNA，通过添加 IFN-γ，其表现出最高的 IDO 诱导作用。另一方面，IDO基因的表达被酪氨酸激酶抑制剂除草霉素A强烈抑制，表明酪氨酸激酶在酶诱导中的作用。 Northern印迹分析表明，除了胎盘、肺和小肠外，人IDO基因在胸腺中大量表达。

项目成果

Osamu Takikawa: "Synergism between IFN-γ and IL-1 α/β in Growth Inhibition of an Allografted Tumor" J.Immunol.151. 2070-2076 (1993)

Osamu Takikawa：“IFN-γ 和 IL-1 α/β 在同种异体移植肿瘤生长抑制中的协同作用”J.Immunol.151（1993）。

Akihiko Kadoya: "Gene Structure of Human Indoleamine 2,3-Dioxygenase" Biochem.Biophy.Res.Commun.189. 530-536 (1992)

Akihiko Kadoya：“人吲哚胺 2,3-双加氧酶的基因结构”Biochem.Biophy.Res.Commun.189。

Tone S., Kadoya A., Maeda H., Minatogawa Y., and Kido R.: "Assignment of the human indoleamine 2,3-dioxygenase gene to chromosome 8 using the polymerase chain reaction" Hum.Genet.93. 201-203 (1994)

Tone S.、Kadoya A.、Maeda H.、Minatokawa Y. 和 Kido R.：“使用聚合酶链反应将人类吲哚胺 2,3-双加氧酶基因分配到 8 号染色体”Hum.Genet.93。

Habara-Ohkubo A., Shirahata T., Takikawa O., and Yoshida R.: "Establishment of an antitoxoplasma state by stable expression of mouse indoleamine 2,3-dioxygenase" Infect.and Immun.61. 1810-1813 (1993)

Habara-Ohkubo A.、Shirahata T.、Takikawa O. 和 Yoshida R.：“通过小鼠吲哚胺 2,3-双加氧酶的稳定表达建立抗弓形虫状态” Infect.and Immun.61。

Akemi Habara‐Ohkubo: "Establishment of Antitoxoplasma State by Stable Expression of Mouse Indoleamine 2,3‐Dioxygenase" Infect.Immun.61. 1810-1813 (1993)

Akemi Habara-Ohkubo：“通过稳定表达小鼠吲哚胺 2,3-双加氧酶来建立抗弓形虫状态”Infect.Immun.61 (1993)。