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

Parul Houston, Callum J. Campbell, John Svaren, Jeffrey Milbrandt, Martin Braddock

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Effective tissue repair results from a rapid, temporally orchestrated series of events. At the site of local tissue injury, the production of many growth factors and cytokines is, in part, stimulated by the early growth response 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 trans-activation of cognate target genes. NAB2 blocks Egr-1 activation of the tissue factor (TF) promoter, Egr-1 stimulated production of PDGF-AB, HGF, TGFβ, and VEGF and the endogenous expression of PDGF-AB and TGFβ. Expression of a wild-type NAB2 but not a dominant negative NAB2 mutant abrogates Egr-1 driven TF promoter activity and tubule formation in an in vitro model of angiogenesis. These findings may have importance in any tissue that is subject to scarring after acute or chronic injury.

Original languageEnglish
Pages (from-to)480-486
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume283
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Angiogenesis
  • Egr-1
  • Gene therapy
  • Growth factor
  • NAB2
  • Tissue repair
  • Transcriptional repressor

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