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ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90

Bui Thi Kim Ly*, Hoang Thanh Chi†‡

* Department of Food Biotechnology, Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City, Vietnam
† Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam
‡ Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam

Oncology Research 2018, 26(8), 1201-1205. https://doi.org/10.3727/096504018X15154104709325

Abstract

FMS-like tyrosine kinase-3 fragments from exon 14 to the end without any mutations or deletions have been reported to fuse to ETV6 (TEL) in a few cases of myeloid/lymphoid neoplasms with eosinophilia carrying a translocation t(12;13)(p13;q12). This fusion protein confers constitutive activation on the FLT3 fragment and induces factor-independent growth in transfected Ba/F3 cells, indicating that it is an oncoprotein. However, the mechanism controlling the stability of this oncoprotein is unknown. In this study, we focus on finding factors controlling the stability of ETV6/FLT3. We have shown that the stability of ETV6/FLT3 is regulated by the Hsp90 chaperone. ETV6/FLT3 fusion protein forms a complex with Hsp90 by coimmunoprecipitation analyses using an Hsp90 antibody. The association between ETV6/FLT3 fusion protein and Hsp90 was impaired after treating ETV6/FLT3 transient transfection cos7 cells with 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG induced a time- and dose-dependent downregulation of ectopically expressed ETV6/FLT3 protein in cos7 and HeLa-transfected cells. By using cycloheximide to block new protein translation, we found that 17-AAG accelerated the decay of ETV6/FLT3. Our findings could contribute to more understanding of the ETV6/FLT3 regulation through Hsp90 chaperone and open the way to finding effective treatment strategies for this rare disease.

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APA Style
Ly, B.T.K., Chi, H.T. (2018). ETV6/FLT3 fusion is a novel client protein of hsp90. Oncology Research, 26(8), 1201-1205. https://doi.org/10.3727/096504018X15154104709325
Vancouver Style
Ly BTK, Chi HT. ETV6/FLT3 fusion is a novel client protein of hsp90. Oncol Res. 2018;26(8):1201-1205 https://doi.org/10.3727/096504018X15154104709325
IEEE Style
B.T.K. Ly and H.T. Chi, "ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90," Oncol. Res., vol. 26, no. 8, pp. 1201-1205. 2018. https://doi.org/10.3727/096504018X15154104709325



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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