Specific role of cytoplasmic dynein in the mechanism of action of an antitumor molecule, Amblyomin-X
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Data
2016
Autores
Pacheco, Mario T. F.
Morais, Katia L. P. [UNIFESP]
Berra, Carolina M.
Demasi, Marilene
Sciani, Juliana M.
Branco, Vania G.
Bosch, Rosemary V.
Iqbal, Asif
Chudzinski-Tavassi, Ana Marisa
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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.
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Experimental Cell Research. San Diego, v. 340, n. 2, p. 248-258, 2016.