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首页> 外文期刊>Biochemistry >The C-Terminus of Nucleolin Promotes the Formation of the c-MYC G-Quadruplex and Inhibits c-MYC Promoter Activity
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The C-Terminus of Nucleolin Promotes the Formation of the c-MYC G-Quadruplex and Inhibits c-MYC Promoter Activity

机译:核仁的C-末端促进C-MYC G-Quadreplex的形成并抑制C-Myc启动子活性

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摘要

Nucleolin, the most abundant nucleolar phosphoprotein of eukaryotic cells, is known primarily for its role in ribosome biogenesis and cell proliferation. It is, however, a multifunctional protein that, depending on the cellular context, can drive either cell proliferation or apoptosis. Our laboratory recently demonstrated that nucleolin can function as a repressor of c-MYC transcription by binding to and stabilizing the formation of a G-quadruplex structure in a region of the c-MYC promoter responsible for controlling 85-90% of c-MYC's transcriptional activity. In this study, we investigate the structural elements of nucleolin that are required for c-MYC repression. The effect of nucleolin deletion mutants on the formation and stability of the c-MYC G-quadruplex, as well as c-MYC transcriptional activity, was assessed by circular dichroism spectropolarimetry, thermal stability, and in vitro transcription. Here we report that nucleolin's RNA binding domains 3 and 4, as well as the arginine-glycine-glycine (RGG) domain, are required to repress c-MYC transcription.
机译:核仁,最丰富的真核细胞的核仁磷蛋白,主要是已知其在核糖体生物发生和细胞增殖中的作用。然而,根据细胞环境,可以推动细胞增殖或细胞凋亡的多功能蛋白质。我们的实验室最近证明,通过结合并稳定负责控制C-MYC的C-MYC的转录的C-MYC启动子区域中的G-Quadflex结构的形成,核素可以作为C-MYC转录的阻遏物。活动。在这项研究中,我们研究了C-MYC镇压所需的核仁核的结构元素。通过圆形二色性分光聚氯乙烯,热稳定性和体外转录,评估核仁缺失突变体对C-MYC G-QUADRUPLEX的形成和稳定性以及C-MYC转录活性的影响。在这里,我们报告说,核仁的RNA结合结构域3和4以及精氨酸 - 甘氨酸 - 甘氨酸(RGG)结构域需要抑制C-MYC转录。

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