The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis.
The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis.
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DOI：
10.1089/dna.2015.2908
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发表时间：
2016-01
影响因子：
3.1
通讯作者：
Wei Wang;Hong-Jie Wang;B. Wang;Y. Li;Yan Qin;Li-shuang Zheng;Jin-sa Zhou;P. Qu;Jian-Hong Shi;Haisheng Zhang
中科院分区：
文献类型：
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作者：
Wei Wang;Hong-Jie Wang;B. Wang;Y. Li;Yan Qin;Li-shuang Zheng;Jin-sa Zhou;P. Qu;Jian-Hong Shi;Haisheng Zhang
多功能转录因子Y-box结合蛋白1 （YB1）的不同结构域通过反激活或抑制各种基因的启动子来调节增殖、分化和凋亡。在这里，我们报道了YB1的c端结构域（YB1 CTD）参与内皮细胞的增殖、凋亡和管的形成。寡核苷酸下拉实验表明，YB1通过125-220个氨基酸直接结合内皮细胞的双链GC盒序列。构建含有绿色荧光蛋白（GFP）或GFP标记的YB1 CTD的腺病毒表达载体，用于感染EA.hy926内皮细胞。过表达YB1 CTD可显著提高p21表达，降低cyclin B1表达，抑制EA.hy926细胞的增殖。YB1 CTD过表达还能增加EA.hy926细胞中Bax和活性caspase 3的表达，降低Bcl-2的表达，诱导细胞凋亡。此外，过表达YB1 CTD可显著抑制EA.hy926细胞的迁移和小管形成。最后，YB1 CTD降低了EA.hy926细胞中ERK1/2的磷酸化。这些发现表明，YB1通过对GC盒相关基因的转录调控，在内皮细胞增殖、凋亡和管形成中发挥重要作用。
Different domains of the multifunctional transcription factor Y-box binding protein 1 (YB1) regulate proliferation, differentiation, and apoptosis by transactivating or repressing the promoters of various genes. Here we report that the C-terminal domain of YB1 (YB1 CTD) is involved in endothelial cell proliferation, apoptosis, and tube formation. The oligo pull-down assays demonstrated that YB1 directly binds double-stranded GC box sequences in endothelial cells through the 125-220 amino acids. Adenovirus expression vectors harboring green fluorescent protein (GFP) or GFP-tagged YB1 CTD were constructed and used to infect EA.hy926 endothelial cells. Overexpression of the YB1 CTD significantly increased p21 expression, decreased cyclin B1 expression, and inhibited the proliferation of EA.hy926 cells. YB1 CTD overexpression also increased Bax and active caspase 3 expression, decreased Bcl-2 expression, and induced apoptosis in EA.hy926 cells. Furthermore, overexpression of the YB1 CTD significantly suppressed migration and tube formation in EA.hy926 cells. Finally, YB1 CTD decreased ERK1/2 phosphorylation in EA.hy926 cells. These findings demonstrated vital roles for YB1 in endothelial cell proliferation, apoptosis, and tube formation through transcriptional regulation of GC box-related genes.