Structure-function analysis of the anti-proliferative effect of the human guanylate binding protein-1 (GBP-1) in endothelial cells

Inflammatory cytokines (IC) are potent inhibitors of endothelial cell proliferation. As a specific mediator of the anti-proliferative effect of IC on endothelial cells (EC) we identified the large GTPase human guanylate binding protein-1 (GBP-1). Ectopic expression of GBP-1 in EC inhibited angiogenic growth factor (AGF)-induced proliferation, whereas inhibition of IC-induced GBP-1 expression by GBP-1 antisense RNA abrogated the anti-proliferative effect of IC. GBP-1 selectively inhibited the proliferation of endothelial cells in the absence of apoptosis and without affecting adhesiveness for monocytes, morphogenesis or ERK 1/2 activation. Structure-function-analysis conveyed that the anti-proliferative effect is mediated specifically by the helical domain of GBP-1 and independent of isoprenylation or GTP-hydrolysis.