Research on Gene Expression Network via histone acetylation

组蛋白乙酰化基因表达网络研究

• 批准号: 12557018
• 负责人: ISHII Shunsuke
• 金额: $ 8.32万
• 依托单位: THE INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557018/
• 关键词: Mutant mice; Transcription factor; Shn-2; Transcriptional corepressor; Ski; Immune system; Cellular transformation; Development; 疾患モデル; 発がん; 形態異常

We have generated and analysed the mutant mice lacking transcription factor Shn-2. Shn-2 was originally identified by our group as a factor that binds to the NF-KB site, and a large protein of 270 kD with two metal-finger structures. Since Drosophila homologue of Shn acts in the dpp signaling pathway, vertebrate Shn is thought to act in the BMP/TGFβ/activin signaling pathway. Shn-2-deficient mice seems to be healthy, but have a defects of T-cell development. In the thimi of Shn-2 mutant mice, almost no single-positive T cells were observed. A series of analyses indicated that Shn-2 is essential for the positive selection of T ceils. These results suggest that the BMP/TGFβ/activin signaling pathway plays some role in the T cell development.We have also analysed the physiological role of Ski by using the Ski-deficient mice. We treated the Ski heterozygous mutant mice with chemical carcinogen DMBA. No tumors were generated in wild-type mice, whereas significant numbers of Ski heterozygotes developed the tumors such as T- and B-cell lymphomas. Further, the mouse fibroblasts prepared from the Ski-deficient embryos had increased proliferative capacity compared to wild-type cells. In addition, the introduction of activated Ki-ras into Ski-deficient mouse embryonic fibroblasts resulted in neoplastic transformation. These finding demonsrrate that Ski acts as a tumor suppressor in some types of cells.

我们已经产生并分析了缺乏转录因子SHN-2的Mitter，并且具有两个金属指的大型蛋白质，自DPP信号传导途径SHN-2-的果蝇同源物带有两个金属手指结构。缺乏小鼠是健康的，但是t-cell发育的缺陷。途径在T细胞发育中起着一定的作用。与野生型细胞相比，YOS增加了增生的质量。细胞。

项目成果

Khan, M.M.et al.: "PML-RARα alleviates the transcriptional repression mediated by tumor suppressor Rb"J. Biol. Chem.. 276. 43491-43494 (2001)

Khan, M.M. 等人：“PML-RARα 减轻肿瘤抑制因子 Rb 介导的转录抑制”J. Biol. 276. 43491-43494 (2001)

Khan, M.M.et al.: "Role of PML and PML-RARα in Mad-mediated transcriptional repression"Molecular Cell. 7. 1233-1243 (2001)

Khan，M.M. 等人：“PML 和 PML-RARα 在 Mad 介导的转录抑制中的作用”《分子细胞》。

Koshiro MONZEN et al.: "Smads, TAK1, and their common target ATF-2 play a critical role in cardiomyocyte differentiation."J. Boil. Chem.. 153. 687-698 (2001)

Koshiro MONZEN 等人：“Smads、TAK1 及其共同靶标 ATF-2 在心肌细胞分化中发挥着关键作用。”

Kenji KOKURA et al: "The Ski family is required for MeCP2-mediated transcriptional repression."J. Boil. Chem.. 276. 34115-34121 (2001)

Kenji KOKURA 等人：“Ski 家族是 MeCP2 介导的转录抑制所必需的。”J.

Md. M. KHAN et al.: "Role of PML and PML-RARα in Mad-mediated transcriptional repression."Molecular Cell. 7. 1233-1243 (2001)

Md. M. KHAN 等人：“PML 和 PML-RARα 在 Mad 介导的转录抑制中的作用”。《分子细胞》7. 1233-1243 (2001)