• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Molecular analysis of transcriptional transactivation by the androgen receptor.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_td_9517563_sip1_m.pdf
    Size:
    2.895Mb
    Format:
    PDF
    Description:
    azu_td_9517563_sip1_m.pdf
    Download
    Author
    Chamberlain, Nancy Louise.
    Issue Date
    1994
    Committee Chair
    Miesfeld, Roger L.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The physiological effects of steroid hormones are mediated through intracellular receptors that regulate transcription of hormone response element (HRE)-containing genes. Although the androgen receptor (AR) and the glucocorticoid receptor (GR) are coexpressed in many tissues and bind identical HREs, biological actions of each hormone are distinct. Elucidating the mechanisms by which AR and GR regulate transcription of their target genes is vital to understanding cell- and receptor-specific effects of steroid hormones. These receptor-specific effects were investigated using a system in which AR and GR differ in their abilities to activate transcription from the same reporter genes. To determine if the differential activity was due to inherent differences between AR and GR functional domains, the activities of AR/GR chimeric receptors were examined. Functional differences in the N-terminal modulatory domains and, to a lesser degree, the DNA binding domains, contributed to the differential transactivation. A panel of AR derivatives was constructed to examine the function of the N-terminal domain of this receptor. The AR modulatory domain contains a tract of glutamine residues encoded by the trinucleotide CAG. Expansion of this trinucleotide repeat is correlated with the incidence and severity of the degenerative neuromuscular syndrome Kennedy's disease. To investigate the relationship of this repeat to AR function, receptors that varied in the presence, position or size of the polyglutamine tract were constructed. Elimination of the tract resulted in elevated transactivation. Progressive expansion of the repeat caused a linear decrease in transcriptional activation. These results indicate the polyglutamine tract is inhibitory to AR transactivation function. Further analysis of the AR modulatory domain revealed two regions are necessary for maximal transactivation. Secondary structure prediction and site-directed mutagenesis of one region suggest a ten residue acidic amphipathic α-helix is critical for activity. The second region may be a member of the proline-rich class of activation domains. Together, these two regions may form an interaction surface that contacts a limiting factor(s) required for activated transcription. Receptor-selective interactions with promoter- or cell-specific auxiliary factors could control the specificity of steroid-regulated gene networks.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Biochemistry
    Graduate College
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.