Screening for signal-responsive genes by an enhancer-trap vector and their application

增强子陷阱载体筛选信号响应基因及其应用

• 批准号: 11357002
• 负责人: NODA Makoto
• 金额: $ 20.16万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11357002/
• 关键词: retroviral vector; TGF-β; TMX; thioredoxin; ER stress; bleomycin; c-IAP2; X-ray-responsive genes; レトロウイルスベクター; エンハンサートラップ; X線; NF-kB; Bax; 遺伝子発現; エンハンサー・トラップ; シグナル伝達; TGF-β

As applications of the newly developed enhancer trap system using a retroviral vector (pROSA-nGBT), we screened genes responsive to TGF-β or bleomycin, succeeded in isolating multiple genes of interest in each case, and could publish a part of these results. One of the TGF-β-responsive genes was found to encode a novel, thioredoxin-related transmembrane protein localized in the endoplasmic reticulum (ER) and was suggested to be a molecule involved in the management of ER stress. One of the genes responsive to bleomycin, a drug inducing DNA double strand break, was identified as C-IAP2 know to be involved in apoptosis. Since the promoter of this gene was found also to respond to therapeutic dosages of ionizing radiation, its application in radiation gene therapy is an interesting possibility and warrants further investigation.

作为使用逆转录病毒载体（pROSA-nGBT）的新开发的增强子捕获系统的应用，我们筛选了对TGF-β或博莱霉素有反应的基因，成功地在每个案例中分离出多个感兴趣的基因，并且可以发表这些结果的一部分。其中一个 TGF-β 反应基因被发现编码一种位于内质网 (ER) 中的新型硫氧还蛋白相关跨膜蛋白，并被认为是参与 ER 应激管理的分子。对博来霉素（一种诱导 DNA 双链断裂的药物）有反应的基因之一被鉴定为 C-IAP2，已知与细胞凋亡有关。由于发现该基因的启动子也对电离辐射的治疗剂量有反应，因此其在放射基因治疗中的应用是一个有趣的可能性，值得进一步研究。

项目成果

秋山暢丈: "Identification of a series of TGF-β-responsive genes by retrovirus-mediated gene-trap screening"Molecular and Cellular Biology. (印刷中).

Nobutake Akiyama：“通过逆转录病毒介导的基因陷阱筛选鉴定一系列 TGF-β 反应基因”《分子和细胞生物学》（出版中）。

松本貴子 ら: "Transient overexpression of NGFI-A gene suppresses NGF-induced neurite outgrowth in PC12 cells"NeuroReport. 11. 1001-1005 (2000)

Takako Matsumoto 等人：“NGFI-A 基因的瞬时过度表达抑制 PC12 细胞中 NGF 诱导的神经突生长”NeuroReport。11. 1001-1005 (2000)

W.Matsuo: "Identifiaction of a novel thioredoxin-related transmembrane protein"J. Biol. Chem.. 276. 10032-10038 (2001)

W.Matsuo：“一种新型硫氧还蛋白相关跨膜蛋白的鉴定”J。

T.Ueda: "c-IAP2 is induced by ionizing radiation through NF-kB biniding sites"FEBS Lett.. 491. 40-44 (2001)

T.Ueda：“c-IAP2 是通过 NF-kB 结合位点的电离辐射诱导的”FEBS Lett.. 491. 40-44 (2001)

Y.Matsuo: "Identifiaction of a novel thioredoxin-related transmembrane protein"J.Biol.Chem.. 276. 10032-10038 (2001)

Y.Matsuo：“新型硫氧还蛋白相关跨膜蛋白的鉴定”J.Biol.Chem.. 276. 10032-10038 (2001)