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Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom*

Yu Song,Ke Gong,Hong-ling Yan,W. Hong,Le Wang,Yingliang Wu,Wenhua Li,Wenxin Li,Zhijian Cao

Published 2014 in Journal of Biological Chemistry

ABSTRACT

Background: Sj7170 is a new peptide from scorpion venom. Results: Sj7170 specifically inhibits the activity of α-chymotrypsin. Sj7170 promotes glioblastoma tumorigenesis and metastasis by up-regulating cyclin D1 and Snail. Conclusion: Sj7170 not only specifically inhibits α-chymotrypsin activity but also promotes the tumorigenesis and metastasis of glioblastoma. Significance: Sj7170 is a unique dual-function peptide with a protease inhibitory activity and a potent tumor-activating effect. A new peptide precursor, termed Sj7170, was characterized from the venomous gland cDNA library of the scorpion Scorpiops jendeki. Sj7170 was deduced to be a 62-amino acid peptide cross-linked by five disulfide bridges. The recombinant Sj7170 peptide (rSj7170) with chromatographic purity was produced by a prokaryotic expression system. Enzyme inhibition assay in vitro and in vivo showed that rSj7170 specifically inhibited the activity of α-chymotrypsin at micromole concentrations. In addition, Sj7170 not only promoted cell proliferation and colony formation by up-regulating the expression of cyclin D1 in vitro but also enhanced tumor growth in nude mice. Finally, Sj7170 accelerated cellular migration and invasion by increasing the expression of the transcription factor Snail and then inducing the epithelial-mesenchymal transition. Moreover, Sj7170 changed cell morphology and cytoskeleton of U87 cells by the GTPase pathway. Taken together, Sj7170 is a unique dual-function peptide, i.e. a specific α-chymotrypsin inhibitor and a potent tumorigenesis/metastasis activator. Our work not only opens an avenue of developing new modulators of tumorigenesis/metastasis from serine protease inhibitors but also strengthens the functional link between protease inhibitors and tumor activators.

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