Studies on Multiple Homeodomain/Zn Finger ATBF1 Gene Family

多同源结构域/锌指ATBF1基因家族的研究

• 批准号: 06044010
• 负责人: NISHI Shinzo
• 金额: $ 5.44万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06044010/
• 关键词: ATBF1; alpha-fetoprotein gene; Transcription factor; Homeotic-domain; Zn-finger structure; Alternative splicing; Neuronal differentiation; Cell growth control; Zn- フィンガー; α-フェトプロテイン; 選択的スプライシング; 神経分化

The ATBF1(AT motif binding factor 1)cDNA was isolated based on the ability of its product to bind to an AT-rich enhancer element of the human alpha-fetoprotein(AFP)gene. This transcription factor is characterized by a large size(>300kd)and presence of many DNA-binding domains(4 homeotic-domain, 22 Zn-finger structure). This protein also contains many other functional domain structures, such as acidic-domain, glutamine-rich domain, ATP-ase-like domain and kination sequence.To understand the structure, expression and physiological functions of this interesting protein, we collaborate with members of different fields. The international collaboration was obtained the following results.1.The mouse ATBF1 was cloned and shows 95% homologies with human. The homeotic domains were conserved at 100%.2.Two isoform of the ATBF1(ATBF1-A and ATBF1-B)were expressed from the independent promoters and alternative splicing. The promoter specific for ATBF1-A controls the neural cell expression.3.The results of in situ-hybridization and Northern blotting analysis of P19 cells indicate that the expression of ATBF1 is closely associate with neuronal differentiation.4.ATBF1 genes of human and mouse were mapped on Chromosome 16p22.3-23.1 and 8E1, respectively.5.ATBF1 suppresses the transcription of AFP gene. The required domains for the suppression were located on proline-rich domain and 4th homeotic-domain.6.We have obtained many other interesting properties of ATBF1, i.e., ATBF1 functions as a dimer, ATBF1 might be processed in nucleus and ATBF1 worked as a suppressor of the cell growth.For keep the close contacts between collaborators and exchange the information, 12 researchers visited to Canada and 4 researchers invited to Japan within 2 years. This collaboration was very successfully functioned and made excellent results as described above.

ATBF1(AT基序结合因子1)是根据其产物与人甲胎蛋白(AFP)基因富含AT的增强子元件结合的能力而分离的。该转录因子具有大小(300kd)和多个DNA结合域(4个同源异型结构域，22个锌指结构)的特征。该蛋白还含有许多其他功能结构域，如酸性结构域、谷氨酰胺富集区、类ATP酶结构域和激活序列。为了了解这个有趣的蛋白的结构、表达和生理功能，我们与不同领域的成员合作。本次国际合作取得了以下成果：1.克隆了小鼠ATBF1基因，与人类ATBF1基因有95%的同源性。ATBF1的两个亚型(ATBF1-A和ATBF1-B)通过独立启动子和选择性剪接获得表达。P19细胞的原位杂交和Northern印迹分析结果表明，ATBF1的表达与神经元分化密切相关。4.人和小鼠的ATBF1基因分别定位在染色体16p22.3-23.1和8e1上。5.ATBF1抑制AFP基因的转录。6.我们还获得了ATBF1的许多有趣的性质，即ATBF1作为二聚体，ATBF1可以在细胞核内加工，ATBF1作为细胞生长抑制因子发挥作用。为了保持合作者之间的密切联系和信息交流，我们在2年内访问了加拿大的12名研究人员和应邀访问日本的4名研究人员。如上所述，这种合作非常成功地发挥了作用，并取得了出色的成果。

项目成果

Ido,A.: "Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control" Cancer Research. 55. 3105-3109 (1995)

Ido,A.：“使用携带单纯疱疹病毒胸苷激酶基因的逆转录病毒载体对肝癌细胞进行基因治疗”癌症研究。

Doroshow,J.H.: "Thansduction of NIH 3T3 cells with a retrovirus carrying both human MDRI and glutathione S-transferasep produces broad-range multidrug" Cancer Research. 55. 4073-4078 (1995)

Doroshow，J.H.：“用携带人类 MDRI 和谷胱甘肽 S-transferasep 的逆转录病毒转导 NIH 3T3 细胞可产生广泛的多药”癌症研究。

Sakai, M.: "Suppression of rat glutathione transferase P expression by peroxisome proliferators" Cancer Research. 55. 5370-5376 (1995)

Sakai, M.：“过氧化物酶体增殖物对大鼠谷胱甘肽转移酶 P 表达的抑制”癌症研究。

Tamaoki, T.: "Gene therapy using regulatory region of the AFP gene" Protein, Nucleic Acid and Enzymes. 40. 2613-2617 (1995)

Tamaoki, T.：“利用 AFP 基因调控区域的基因治疗”蛋白质、核酸和酶。

Saegusa, M.: "Down-regulation of human α-fetoprotein promoter by c-jun and c-fos." J. Tumor Marker Oncol.9. 29-33 (1994)

Saegusa, M.：“c-jun 和 c-fos 下调人甲胎蛋白启动子。J. Tumor Marker Oncol.9 (1994)。