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Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor.

Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Research Abstract Details 

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  • Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Abstract Text:

    kenneth robzykKenneth Robzyk,handy oenHandy Oen,grant buchananGrant Buchanan,lisa m butlerLisa M Butler,wayne d tilleyWayne D Tilley,atin k mandalAtin K Mandal,neal rosenNeal Rosen,avrom j caplanAvrom J Caplan,

    The mechanisms underlying androgen receptor (AR)-mediated progression of prostate cancer following androgen ablation have yet to be fully determined. On this basis we screened naturally occurring mutants of human AR for hormone-independent activity using a yeast model system. An initial screen of 43 different mutants revealed that ARs having a Leu701His mutation (AR(L701H)) exhibited hormone-independent activation of a lacZ reporter gene. The AR(L701H) mutant bound dihydrotestosterone to a similar extent as did wild type AR, although its ability to be induced by hormone for transactivation was reduced substantially. Subsequent studies focused on the dependence of AR(L701H) on molecular chaperones for folding to the active state. We found that AR(L701H) was highly dependent on Hsp90 for its hormone-independent activation, suggesting that this chaperone functions in AR(L701H) folding. However, the mutant did not respond specifically to increased levels of FKBP52, suggesting that this chaperone functions at the hormone-dependent activation stage in the folding process. Further studies of AR(L701H) in PC3 cells suggested that this mutant is prohibited from hormone-independent transactivation in mammalian cells. However, basal expression of a reporter gene by AR(L701H) was not impaired by the presence of 17-allylamino-17-demethoxygeldanamycin as was wild type AR, suggesting differential interactions of these receptors with molecular chaperones in animal cells.

    Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Publishing Authors By Initials

    k robzykK Robzyk,h oenH Oen,g buchananG Buchanan,lm butlerLM Butler,wd tilleyWD Tilley,ak mandalAK Mandal,n rosenN Rosen,aj caplanAJ Caplan,

    For similar fungi: yeasts research abstracts see: fungi: yeasts research

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    Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Molecular and cellular endocrinology

    VOLUME: 268

    Page Numbers: 67-74

    Journal Abbreviation: Mol. Cell. Endocrinol.

    ISSN: 0303-7207

    DAY: 6

    MONTH: 02

    YEAR: 2007

    Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7500844

    Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Keywords Mesh Terms:

    KEYWORDS: Yeasts

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Information

    Substance Name: Histidine

    Registry Number: 71-00-1

    Grant and Affiliation Information for Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor.

    AFFILIATION: Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

    Country: Ireland

    Ireland Research PublicationIreland Research Publication

    AGENCY: United States NIGMS

    GRANT: R01 GM070596-03

    ACRONYM: GM

    MEDLINETA: Mol Cell Endocrinol

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