Tomato cystine-knot miniproteins: purification and new insights into the molecular mechanisms of their anti-angiogenic properties

In a previous study we identified two tomato cystin e-knot miniproteins (TCMP-1 and -2) potentially endowed with biological activities. We described their antiangiogenic properties in vitro , with inhibition of endothelial tube formation and cell migration induced by epidermal growth factor (EGF), associated with inhibition of ERK 1/2 phosphorylation (Cavallini et al. Br J Pharmacol 2011;162:1261-73). TCMPs belong to a large family of cysteine-rich proteins characterized by three intramolecular disulfide bon ds forming a structural motif called cystine-knot. These proteins are widespread in euka ryotes and are being characterised for a broad spectrum of therapeutical activities (Kolmar H. Curr Pharm Des 2011;17:4329-36). The present study aims to further characterize and give a mechanistic insight into the anti- angiogenic activity of the cystine-knot miniprotein which is most abundant in mature tomato fruit (TCMP-2).