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Updated: Jun 26, 2026
11:32
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Transcription factor 8 activates R-Ras to regulate angiogenesis.
Takayuki Inuzuka1, Masumi Tsuda, Hideaki Kawaguchi
1Laboratory of Pathophysiology and Signal Transduction, Hokkaido University, Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan.
Biochemical and Biophysical Research Communications
|January 1, 2009
Summary
Transcription factor 8 (TCF8) suppresses pathological angiogenesis by activating R-Ras through cytosolic interaction with CalDAG-GEFIII. This novel mechanism reveals TCF8
Area of Science:
- Molecular Biology
- Cell Biology
- Angiogenesis Research
Background:
- Transcription factor 8 (TCF8) is known to negatively regulate pathological angiogenesis.
- TCF8's role in modulating cell adhesion is established, but its precise molecular mechanisms remain unclear.
- Previous work identified TCF8 as a transcriptional attenuator of matrix metalloproteinase 1.
Purpose of the Study:
- To elucidate the molecular mechanism by which TCF8 suppresses angiogenesis beyond its transcriptional role.
- To investigate TCF8's interaction with other angiogenic regulators, specifically R-Ras.
- To understand how TCF8 influences endothelial cell behavior in angiogenesis.
Main Methods:
- Investigated TCF8's effect on R-Ras activation in endothelial cells.
- Utilized constitutive active mutant of R-Ras to assess its impact on TCF8-mediated angiogenesis.
- Examined mRNA expression levels of R-Ras regulators.
- Performed co-immunoprecipitation to detect TCF8 binding to CalDAG-GEFIII in the cytosol.
Main Results:
- TCF8 activates R-Ras to suppress angiogenesis via a non-transcriptional attenuator mechanism.
- Suppression of TCF8 led to increased tube formation in human umbilical vein endothelial cells (HUVECs), which was inhibited by active R-Ras.
- No significant changes in mRNA levels of R-Ras regulators were observed.
- TCF8 was found to bind CalDAG-GEFIII, an R-Ras activator, within the cytosol.
Conclusions:
- TCF8 negatively regulates angiogenesis by activating R-Ras through a novel cytosolic signaling pathway involving CalDAG-GEFIII.
- This finding expands the understanding of TCF8's function in angiogenesis and cell signaling.
- TCF8's cytosolic interaction with CalDAG-GEFIII provides a new target for therapeutic intervention in angiogenesis-related diseases.
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