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

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

Author Pacheco, Mario T. F. Google Scholar
Morais, Katia L. P. Autor UNIFESP Google Scholar
Berra, Carolina M. Google Scholar
Demasi, Marilene Google Scholar
Sciani, Juliana M. Google Scholar
Branco, Vania G. Google Scholar
Bosch, Rosemary V. Google Scholar
Iqbal, Asif Google Scholar
Chudzinski-Tavassi, Ana Marisa Google Scholar
Abstract 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.
Keywords Amblyomin-X
Dynein
Proteasome
Plasma membrane
Cancer
Endocytosis
Autophagy
Apoptosis
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
Grant number FAPESP: 2000/11624-5
FAPESP: 2011/05969-4
FAPESP: 2010/07958-7
FAPESP: CETICs 2013/07467-1
Date 2016
Published in Experimental Cell Research. San Diego, v. 340, n. 2, p. 248-258, 2016.
ISSN 0014-4827 (Sherpa/Romeo, impact factor)
Publisher Elsevier Inc
Extent 248-258
Origin https://doi.org/10.1016/j.yexcr.2015.12.016
Access rights Closed access
Type Article
Web of Science ID WOS:000370581800013
URI https://repositorio.unifesp.br/handle/11600/58552

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