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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Specific role of cytoplasmic dynein in the mechanism of action of an antitumor molecule, Amblyomin-X

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Pacheco, Mario T. F. [1] ; Morais, Katia L. P. [2, 1] ; Berra, Carolina M. [3] ; Demasi, Marilene [1] ; Sciani, Juliana M. [1] ; Branco, Vania G. [1] ; Bosch, Rosemary V. [1] ; Iqbal, Asif [1] ; Chudzinski-Tavassi, Ana Marisa [1]
Total Authors: 9
[1] Butantan Inst, Biochem & Biophys Lab, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Biochem, Inst Chem, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Experimental Cell Research; v. 340, n. 2, p. 248-258, JAN 15 2016.
Web of Science Citations: 7

The Kunitz-type recombinant protein, Amblyomin-X, is an antitumor recombinant molecule from a cDNA library prepared from the salivary glands of the tick Amblyomma cajennense. The primary target of this protein appears to be the proteasome. Amblyomin-X increased gene and protein expression of distinct subunits of the molecular motor dynein, which plays a key role in the intracellular transport. Herein, Amblyomin-X was specifically taken up by tumor cells through lipid-raft endocytic pathways, but not by fibroblasts. Moreover, dynein inhibitor, ciliobrevin A, decreased Amblyomin-X uptake by tumor cells. Furthermore, incubation of tumor cells with Amblyomin-X inhibited trypsin-like activity of the proteasome, which was restored upon pretreatment with ciliobrevin A. Only in tumor cells treated with Amblyomin-X, we identified proteins bounds to dynein that are related to aggresome formation, autophagy inhibition, and early and recycling endosome markers. In addition, Amblyomin-X was found to interact with dynein, increased Rab11A protein expression and Rab11A co-localization with the light intermediate chain 2 (LIC2) of dynein. Thereby, the results provide new insights on the antitumor mechanism of Amblyomin-X and reveal an unsuspected role of cytoplasmic dynein in its uptake, intracellular trafficking and pro-apoptotic action. (C) 2016 Published by Elsevier Inc. (AU)

Grantee:Kátia Luciano Pereira Morais
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
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)