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

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 (GABP gamma) associates with the cytoplasmic domain of BAI2, and GABP alpha/gamma or GABP alpha/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 GABP alpha and GABP gamma elicited increased VEGF expression before the onset of HIF-1 alpha. Our results point out that BAI2 controls VEGF transcription through GABP under normal conditions and cerebral ischemia. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.