• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Regulation of PP2Ac stability – discovery of a novel α4 monoubiquitination-dependent mechanism that is altered in Alzheimer’s disease

    Watkins, Guy Richard
    : https://etd.library.vanderbilt.edu/etd-08062012-134256
    http://hdl.handle.net/1803/13840
    : 2012-12-01

    Abstract

    Studies described in this thesis identify a novel mechanism for α4’s regulation of PP2Ac stability. α4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of α4 triggers calpain-mediated cleavage at the F255-G256 bond in α4 releasing α4 from MID1. The cleavage of α4 switches its activity from protective to destructive towards PP2A, and results in the increase in phosphorylation of the microtubule-associated protein (MAP) tau. This regulatory mechanism appears important in MAP-dependent pathologies as levels of cleaved α4 are decreased in Opitz Syndrome (OS) and increased in Alzheimer’s disease (AD), disorders characterized by MAP hypophosphorylation and hyperphosphorylation, respectively. These findings indicate that regulated inter-domain cleavage controls the dual functions of α4, and dysregulation of α4 cleavage may contribute to OS and AD.
    Show full item record

    Files in this item

    Icon
    Name:
    Watkins-dissertation.pdf
    Size:
    3.091Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy