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    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
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    • 2008 Dissertations (MU)
    • 2008 MU dissertations - Access restricted to MU
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    Functional studies of hCTR1, a high affinity human copper and cisplatin transporter

    Fulcher, Yan G., 1978-
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    [PDF] research.pdf (7.576Mb)
    Date
    2008
    Format
    Thesis
    Metadata
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Copper is an essential nutrient. The uptake of copper is mediated by the human copper transporter 1 (hCTR1) protein at the plasma membrane. Elevated copper concentrations stimulate the endocytosis and degradation of the hCTR1 protein as a control mechanism to prevent excessive copper uptake. Recent studies uncovered a role for the hCTR1 copper importer in the uptake of the chemotherapeutic anticancer drug, cisplatin. Cisplatin shares little structural similarity with copper, and the mechanism of cisplatin uptake via hCTR1 is poorly understood. In this study, I identified several methionine-rich motifs that are likely to function in copper sensing which are critical for aspects of hCTR1 function including copper stimulated endocytosis and degradation. These same motifs are critical for binding cisplatin which cross-links hCTR1 via these motifs. By discovering an endocytosis motif, I also demonstrate that the mechanism of cisplatin requires endocytosis, which is distinct from the permease mechanism of copper uptake. In summary, my research identified important copper sensing domains in the hCTR1 and identified disparate mechanisms controlling the uptake of copper and cisplatin.
    URI
    https://doi.org/10.32469/10355/6048
    https://hdl.handle.net/10355/6048
    Degree
    Ph. D.
    Thesis Department
    Nutrition area program (MU)
    Rights
    Access is limited to the campus of the University of Missouri--Columbia.
    Collections
    • Nutrition and Exercise Physiology electronic theses and dissertations (MU)
    • 2008 MU dissertations - Access restricted to MU

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