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
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
DNA material |
pCMV-VSV-G-RSV-REV (RDB04393) |