Open AccessContributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity
Author(s) -
Annerleim Walton-Diaz,
Sahar Khan,
Dimitra Bourboulia,
Jane B. Trepel,
Len Neckers,
Mehdi Mollapour
Publication year - 2013
Publication title -
future medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.708
H-Index - 69
eISSN - 1756-8927
pISSN - 1756-8919
DOI - 10.4155/fmc.13.88
Subject(s) - hsp90 , chaperone (clinical) , co chaperone , chemistry , atp hydrolysis , drug , drug discovery , biochemistry , atpase , biology , enzyme , microbiology and biotechnology , cancer research , heat shock protein , pharmacology , medicine , pathology , gene
Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.