The transcriptional corepressor NAB2 blocks Egr-1-mediated growth factor activation and angiogenesis

Effective tissue repair results from a rapid, temporally orchestrated serie s of events. At the site of local tissue injury, the production of many gro wth factors and cytokines is, in part, stimulated by the early growth respo nse transcription factors such as Egr-1, Egr-1 protein binds to a family of corepressor proteins called NAB which function to block or limit Egr-1 tra ns-activation of cognate target genes. NABS blocks Egr-1 activation of the tissue factor (TF) promoter, Egr-1 stimulated production of PDGF-AB, HGF, T GF beta (1), and VEGF and the endogenous expression of PDGF-AB and TGF beta (1). Expression of a wild-type NABS hut not a dominant negative NABS mutan t abrogates Egr-1 driven TF promoter activity and tubule formation in an in vitro model of angiogenesis. These findings may have importance in any tis sue that is subject to scarring after acute or chronic injury. (C) 2001 Aca demic Press.