Transcription factor 8 activates R-Ras to regulate angiogenesis
Transcription factor 8 activates R-Ras to regulate angiogenesis
复制标题
DOI：
10.1016/j.bbrc.2008.12.101
复制
发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Ohba, Yusuke
中科院分区：
文献类型：
--
作者：
Inuzuka, Takayuki;Tsuda, Masumi;Ohba, Yusuke
我们最近报道，转录因子8（TCF 8）负调节病理性血管生成，通过调节内皮细胞的侵袭性作为一个转录衰减基质金属蛋白酶1。TCF8还调节细胞-基质和细胞-细胞粘附;然而，这种TCF8功能的分子机制仍然不清楚。在这里，我们提供的证据表明，TCF8激活R-Ras，另一类血管生成调节因子，抑制血管生成的转录衰减剂以外的机制。R-Ras组成型活性突变体的表达显著抑制了TCF8抑制促进的人脐静脉内皮细胞（HUVECs）的管形成。当我们检查R-Ras调节因子的mRNA表达水平时，没有观察到可以解释TCF 8激活R-Ras的显着变化。有趣的是，我们发现TCF 8在胞质溶胶中与R-Ras激活剂CalDAG-GEFIIII结合，表明TCF 8从胞质溶胶中发出R-Ras激活信号以负向调节血管生成。(C)2008年爱思唯尔公司All rights reserved.
We have recently reported that transcription factor 8 (TCF8) negatively regulates pathological angiogenesis by regulating endothelial invasiveness by acting as a transcriptional attenuator of matrix metalloproteinase 1. TCF8 also modulates cell-matrix and cell-cell adhesion; however molecular mechanism of this TCF8 function remains obscure. Here, we provide evidence that TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator. Tube formation by human umbilical vein endothelial cells (HUVECs) facilitated by TCF8 suppression was significantly inhibited by the expression of constitutive active mutant of R-Ras. When we examined the mRNA expression levels of R-Ras regulators, no significant changes were observed to explain the R-Ras activation by TCF8. Interestingly, we found that TCF8 bound to CalDAG-GEFIII, an R-Ras activator, in the cytosol, indicating that TCF8 emanates signaling for R-Ras activation from cytosol to regulate angiogenesis negatively. (C) 2008 Elsevier Inc. All rights reserved.