Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor

FEBS Lett. 2006 Jan 23;580(2):669-76. doi: 10.1016/j.febslet.2005.12.086. Epub 2006 Jan 6.


Previously, we reported that decreased brain-specific angiogenesis inhibitor 2 (BAI2) induced increased VEGF expression. The regulatory mechanisms for this process are not understood. Here we show that GA-binding protein gamma (GABPgamma) associates with the cytoplasmic domain of BAI2, and GABPalpha/gamma or GABPalpha/beta works as a transcriptional repressor of VEGF in SHSY5Y cells. Transcriptional activity of wild-type VEGF promoter was significantly increased in anti-sense BAI2-transfected cells, but not that of VEGF promoter harboring mutated GABP sites. In in vivo focal cerebral ischemia model, the decrease in BAI2 accompanied by decreased GABPalpha and GABPgamma elicited increased VEGF expression before the onset of HIF-1alpha. Our results point out that BAI2 controls VEGF transcription through GABP under normal conditions and cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Cell Line
  • GA-Binding Protein Transcription Factor / genetics
  • GA-Binding Protein Transcription Factor / metabolism*
  • Humans
  • Membrane Proteins
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*
  • Two-Hybrid System Techniques
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • Adgrb2 protein, mouse
  • GA-Binding Protein Transcription Factor
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Subunits
  • Repressor Proteins
  • Vascular Endothelial Growth Factor A