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Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity

    Annerleim Walton-Diaz

    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892–1107, USA

    ,
    Sahar Khan

    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892–1107, USA

    ,
    Dimitra Bourboulia

    Department of Biochemistry & Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA

    Department of Urology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA

    ,
    Jane B Trepel

    Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892–1107, USA

    ,
    Len Neckers

    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892–1107, USA

    &
    Mehdi Mollapour

    * Author for correspondence

    Department of Biochemistry & Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.

    Department of Urology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA

    Published Online:https://doi.org/10.4155/fmc.13.88

    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.

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