CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation
CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation
复制标题
DOI：
10.1096/fj.13-236216
复制
发表时间：
2014-02-01
期刊：
影响因子：
4.8
通讯作者：
Choi, Kang-Yell
中科院分区：
文献类型：
--
作者：
Kim, Hyun-Yi;Yang, Dong-Hwa;Choi, Kang-Yell
CXXC5是含有CXXC型锌指结构域的一小部分蛋白质中的一员。在这里，我们证明CXXC5是一种转录因子，激活血管内皮生长因子受体Flk-1。在小鼠胚胎干细胞内皮细胞分化过程中，CXXC5和Flk-1分别聚集在胞核和胞膜中。CXXC5过表达可诱导内皮细胞分化的MESCs和人脐静脉内皮细胞(HUVECs)转录Flk-1。体外DNA结合实验表明，CXXC5与Flk-1启动子区域直接相互作用，DNA结合基序突变使转录活性丧失。我们发现骨形态发生蛋白4(BMP4)可诱导细胞内CXXC5的转录，BMP信号转导的抑制剂可抑制BMP4对CXXC5的诱导和随后的Flk-1的诱导。CXXC5基因敲除可抑制BMP4诱导的应力纤维形成(56.8+/-1.3%，P
CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accmulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgeneic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8 +/- 1.3% decrease, P