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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 340, n. 2, p. 248-258, JAN 15 2016.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 10/07958-7 - Avaliação do mecanismo de ação pró-apoptótica do amblyomin-x
• Beneficiário: Kátia Luciano Pereira Morais
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 00/11624-5 - Embriologia de Gastropoda: análise em microscopia de varredura laser confocal
• Beneficiário: Toshie Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 11/05969-4 - Estudo do papel da dineína no mecanismo de ação antitumoral do Amblyomin-X em células de melanoma e adenocarcinoma de pâncreas
• Beneficiário: Mario Thiego Fernandes Pacheco
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto