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    • Graduate School - MU Theses and Dissertations (MU)
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    • 2007 Dissertations (MU)
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    Molecular and cell biological studies of mammalian zinc transporters

    Mao, Xiaoqing, 1972-
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    [PDF] research.pdf (3.634Mb)
    Date
    2007
    Format
    Thesis
    Metadata
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Zinc is an essential trace element in all organisms. The importance of the hZIP4 human zinc transporter is highlighted by its causative role in a genetic disease of zinc deficiency, acrodermatitis enteropathica (AE). The overall goal of my project is to understand the cellular and molecular mechanisms of hZIP4 post-translational regulation. The abundance of hZIP4 on the plasma membrane is dependent on zinc availability, and hZIP4 undergoes zinc-stimulated endocytosis. More importantly, an additional level of hZIP4 post-translational regulation was identified, which involves ubiquitination and degradation of this protein by elevated zinc treatments. Furthermore, endocytosis is a prerequisite for its degradation requiring both proteasomes and lysosomes. One characteristic feature of many ZIP proteins is the intracellular histidine-rich region between transmembrane domains 3 and 4. The essentiality of the histidine-rich segment for ubiquitin-mediated degradation of hZIP4 was demonstrated. It functions to prevent cell toxicity from zinc overload. Furthermore, a cytosolic lysine residue is solely responsible for hZIP4 ubiquitination. However, mutation of this lysine does not interfere with zinc-stimulated hZIP4 degradation, suggesting the existence of alternative degradation pathways independent of ubiquitination. The implication that hZIP4 has multiple degradation pathways may provide a precise system regulating hZIP4 protein levels to avoid zinc overload, accounting for the essential role of hZIP4 in achieving zinc homeostasis.
    URI
    https://doi.org/10.32469/10355/6023
    https://hdl.handle.net/10355/6023
    Degree
    Ph. D.
    Thesis Department
    Biochemistry (Agriculture) (MU)
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    Access is limited to the campuses of the University of Missouri.
    Collections
    • 2007 MU dissertations - Access restricted to UM
    • Biochemistry electronic theses and dissertations (MU)
    • Biochemistry electronic theses and dissertations (MU)

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