HIV-tat protein is a hepai in-binding angiogenic growth factor

Adriana Albini, Roberto Benelli, Marco Presta, Marco Rusnati, Marina Ziche, Anna Rubartelli, Giuseppina Paglialunga, Federico Bussolino, Douglas Noonan

Research output: Contribution to journalArticle

Abstract

Transgenic animal studies have linked the expression of the HIV-1 tat gene to the appearance of Kaposi's sarcoma (KS)-like lesions. We have recently shown that recombinant tat is angiogenic in vivo, and that tat angiogenic response is enhanced by heparin. Also in the rabbit cornea model, recombinant HIV-1 tat alone is poorly angiogenic, but gives a good response when combined with heparin. Like many angiogenic growth factors, tat has a basic domain similar to that of several heparin binding angiogenic factors, including FGF, VEGF and HGF, suggesting that this region is important in endothelial cell activation. We show that tat binds heparin sepharose with a high affinity, similar to bFGF. Binding of tat to the cell surface is also modulated by heparin. Biological activities of tat, such as induction of endothelial cell growth, migration and invasion in vitro are all enhanced by low concentrations and inhibited by high concentrations of heparin, as has been shown for other heparin-binding angiogenic factors. Heparan sulfate is also effective, whereas the unsulfated polysaccharide K5 does not enhance tat activity. Furthermore, a peptide encompassing the tat basic domain is able to induce growth and migration of endothelial cells, while an adjacent peptide is not. Our data indicate that the tat basic domain plays a key role in its vascular cell activation properties, and strongly suggest that extracellular HIV-tat is essentially a 'new' heparin-binding angiogenic factor.

Original languageEnglish
Pages (from-to)289-297
Number of pages9
JournalOncogene
Volume12
Issue number2
Publication statusPublished - 1996

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Keywords

  • Angiogenesis
  • Growth factor
  • Heparin
  • HIV
  • Tat

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Albini, A., Benelli, R., Presta, M., Rusnati, M., Ziche, M., Rubartelli, A., Paglialunga, G., Bussolino, F., & Noonan, D. (1996). HIV-tat protein is a hepai in-binding angiogenic growth factor. Oncogene, 12(2), 289-297.