ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90.

Oncology Research
Bui Thi Kim Ly, Hoang Thanh Chi

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 ...Continue Reading

References

Sep 3, 2003·Nature Reviews. Cancer·Derek L Stirewalt, Jerald P Radich
Apr 7, 2009·Biochemical and Biophysical Research Communications·Hoang Anh VuYuko Sato
Jul 11, 2013·PloS One·Bui Thi Kim LyToshiki Watanabe

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Citations

May 9, 2019·Physiological Reviews·Julhash U Kazi, Lars Rönnstrand

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Methods Mentioned

BETA
transfection
immunoprecipitation

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