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ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90

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 t...

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Autores principales: Ly, Bui Thi Kim, Chi, Hoang Thanh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844643/
https://www.ncbi.nlm.nih.gov/pubmed/29471895
http://dx.doi.org/10.3727/096504018X15154104709325
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author Ly, Bui Thi Kim
Chi, Hoang Thanh
author_facet Ly, Bui Thi Kim
Chi, Hoang Thanh
author_sort Ly, Bui Thi Kim
collection PubMed
description 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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spelling pubmed-78446432021-02-16 ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90 Ly, Bui Thi Kim Chi, Hoang Thanh Oncol Res Article 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. Cognizant Communication Corporation 2018-09-14 /pmc/articles/PMC7844643/ /pubmed/29471895 http://dx.doi.org/10.3727/096504018X15154104709325 Text en Copyright © 2018 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Ly, Bui Thi Kim
Chi, Hoang Thanh
ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title_full ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title_fullStr ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title_full_unstemmed ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title_short ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90
title_sort etv6/flt3 fusion is a novel client protein of hsp90
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844643/
https://www.ncbi.nlm.nih.gov/pubmed/29471895
http://dx.doi.org/10.3727/096504018X15154104709325
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