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 (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.
Jeong
Byung Chul
BC
Department of Pharmacology, Research Institute of Medical Sciences, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Dong-Ku, Kwangju 501-190, Republic of Korea.
Kim
Mi-Young
MY
Lee
Ji Hee
JH
Kee
Hae Jin
HJ
Kho
Dhong Hyo
DH
Han
Kae Eun
KE
Qian
Yong Ri
YR
Kim
Jong-Keun
JK
Kim
Kyung Keun
KK
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C484728:Adgrb2 protein, mouse; D051268:GA-Binding Protein Transcription Factor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012097:Repressor Proteins; D042461:Vascular Endothelial Growth Factor A