Rational development of a novel TFPI-like inhibitor from Amblyomma cajennense tick

Author(s)

Morais, Katia L. P. ; Mesquita Pasqualoto, Kerly Fernanda ; Fernandes Pacheco, Mario Thiego ; Berra, Carolina Maria ; Alvarez-Flores, Miryam Paola ; Chudzinski-Tavassi, Ana Marisa

• Document type: Journal article
• Source: Toxin Reviews; v. 33, n. 1-2, p. 5-pg., 2014-03-01.

Abstract

Hematophagous organisms have been described to possess specific blood coagulation inhibitors with different structures and novel mechanism of action. A factor Xa inhibitor was identified through the salivary glands transcriptome from the adult Amblyomma cajennense tick. The recombinant form was expressed in Escherichia coli and named Amblyomin-X. The recombinant protein not only inhibits factor X, but is also able to inhibit the activation of factor X by the extrinsic tenase complex. It seems to activate the apoptosis pathway through proteasome inhibition and endoplasmic reticulum-stress. It promotes regression and reduction of lung metastasis in murine melanoma tumor, and does not affect normal cells, emphasizing its selectivity of action. (AU)

• FAPESP's process: 11/05969-4 - Investigating the role of dynein in the mechanism of antitumor action of Amblyomin-X in melanoma cells and pancreatic adenocarcinoma
• Grantee: Mario Thiego Fernandes Pacheco
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 10/07958-7 - EVALUATION OF THE PRO-APOPTOTIC MECHANISM OF ACTION OF THE AMBLYOMIN-X
• Grantee: Kátia Luciano Pereira Morais
• Support Opportunities: Scholarships in Brazil - Doctorate