RRC ID 5818
Author Inuzuka T, Tsuda M, Kawaguchi H, Ohba Y.
Title Transcription factor 8 activates R-Ras to regulate angiogenesis.
Journal Biochem Biophys Res Commun
Abstract 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.
Volume 379(2)
Pages 510-3
Published 2009-2-6
DOI 10.1016/j.bbrc.2008.12.101
PII S0006-291X(08)02508-4
PMID 19116136
MeSH Cells, Cultured Endothelium, Vascular / cytology Endothelium, Vascular / enzymology Enzyme Activation Guanine Nucleotide Exchange Factors / metabolism Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Mutation Neovascularization, Physiologic* / genetics Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* Umbilical Veins / cytology Umbilical Veins / enzymology Zinc Finger E-box-Binding Homeobox 1 ras Guanine Nucleotide Exchange Factors ras Proteins / genetics ras Proteins / metabolism*
IF 2.985
Times Cited 23
DNA material pCMV-VSV-G-RSV-REV (RDB04393)