Functions of transcription elongation factor S-II for cell stress response and development

转录延伸因子S-II在细胞应激反应和发育中的功能

• 批准号: 14207097
• 负责人: SEKIMIZU Kazuhisa
• 金额: $ 29.12万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207097/
• 关键词: transcription factor; S-II; RNA polymerase II; development; gene knock-out; yeast cells; yeast two hybrid method; erythro differentiation; 遺伝子ノックアウトマウス; イースト2ハイブリッド法; マウス; 胎生致死; 酸化ストレス; 酸化型損傷塩基; 転写忠実度維持

S-II was originally identified as a stimulatory factor of RNA polymerase II in vitro. We have been studying biology of this protein for more than 30 years. Nowadays, S-II is recognized as a transcription elongation factor ubiquitously present in eukaryotic cells. A number of researchers are now studying a role of S-II in eukaryotic transcription. It has been proposed that 5-11 plays an important role on the regulation of transcription in eukaryotic cells. However, there is no direct evidence supporting this notion.The purpose of this project was to test a hypothesis that. S-II plays a role in oxidative stress response in cells. We also hypothesized that S-II is essential for development. We examined phenotypes of yeast cells and mice whose S-II genes were deleted by homologous recombination technique. We showed that yeast deletion mutant of the S-II gene showed higher sensitivity to oxidative stress. We also demonstrated that fidelity of transcription decreased in the mutant. Oxidative stress may cause oxidization of nucleotides that are substrates for RNA synthesis. Furthermore, embryos of mice deletion mutant of the S-II gene showed lethality at early stage of development. We found that the mutant showed abnormal phenotype in erythro differentiation. These results supports our hypothesis that S-II is important for tolerance to oxidative stress and is essential for development of individual bodies.

S-II最初被鉴定为RNA聚合酶II的体外刺激因子。我们已经研究这种蛋白质的生物学超过30年了。如今，S-II被认为是一种转录延伸因子，广泛存在于真核细胞中。许多研究人员现在正在研究S-II在真核转录中的作用。已经提出5-11在真核细胞中的转录调控中起重要作用。然而，没有直接的证据支持这一观点。这个项目的目的是检验一个假设，即。S-II在细胞的氧化应激反应中起作用。我们还假设S-II对发育至关重要。我们检测了酵母细胞和小鼠的表型，其S-II基因被删除的同源重组技术。我们发现，酵母S-II基因的缺失突变体表现出更高的敏感性，氧化应激。我们还证明了在突变体中转录的保真度降低。氧化应激可引起作为RNA合成的底物的核苷酸的氧化。此外，S-II基因缺失突变小鼠的胚胎在发育的早期阶段显示出致死性。我们发现该突变体在细胞分化中表现出异常的表型。这些结果支持了我们的假设，S-II是重要的耐受氧化应激，是必不可少的个人机构的发展。

项目成果

Fukuma et al.: "A role of the Duffy antigen for the maintenance of plasma chemokine concentrations"Biochem Biophys Res Commun. (in press). (2003)

Fukuma 等人：“达菲抗原对于维持血浆趋化因子浓度的作用”Biochem Biophys Res Commun。

Hossain et al.: "ICRF-193, a catalytic inhibitor of DNA topoisomerase II, inhibits re-entry into the cell division cycle form quiescent state in mammalian cells"Gene to Cells. 7. 285-294 (2002)

Hossain 等人：“ICRF-193 是 DNA 拓扑异构酶 II 的催化抑制剂，可抑制哺乳动物细胞从静止状态重新进入细胞分裂周期”Gene to Cells。

T.Ubukata, T.Shimizu, N.Adachi, K.Sekimizu, T.Nakanishi: "Cleavage, but not read-through, stimulation activity is responsible for three biologic functions of transcription elongation factor S-II."J Biol Chem. 278. 8580-8585 (2003)

T.Ubukata、T.Shimizu、N.Adachi、K.Sekimizu、T.Nakanishi：“转录延伸因子 S-II 的三种生物学功能是由切割而非通读刺激活性引起的。”J Biol Chem。

K.Saso, T.Ito, S.Natori, K.Sekimizu: "Identification of a novel tissue-specific transcriptional activator FESTA as a protein that interacts with the transcription elongation factor S-II"J Biochem (Tokyo). 133. 493-500 (2003)

K.Saso、T.Ito、S.Natori、K.Sekimizu：“鉴定一种新型组织特异性转录激活剂 FESTA 作为与转录延伸因子 S-II 相互作用的蛋白质”J Biochem（东京）。

T.Nakanishi, K.Sekimizu: "SDT1/SSM1, a multicopy suppressor of S-II null mutant, encodes a novel pyrimidine 5'-nucleotidase"J Biol Chem. 277. 22103-22106 (2002)

T.Nakanishi，K.Sekimizu：“SDT1/SSM1，S-II 无效突变体的多拷贝抑制子，编码一种新型嘧啶 5-核苷酸酶”J Biol Chem。