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    The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

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    Peterson_2012.pdf (693.6Kb)
    Issue Date
    2012-06-04
    Author
    Peterson, Laura B.
    Eskew, Jeffrey D.
    Vielhauer, George A.
    Blagg, Brian S. J.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/mp300138n
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    Abstract
    Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90β, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effects
    URI
    http://hdl.handle.net/1808/24075
    DOI
    https://doi.org/10.1021/mp300138n
    Collections
    • Medicinal Chemistry Scholarly Works [248]
    Citation
    Peterson, L. B., Eskew, J. D., Vielhauer, G. A., & Blagg, B. S. J. (2012). The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking. Molecular Pharmaceutics, 9(6), 1841–1846. http://doi.org/10.1021/mp300138n

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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