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dc.contributor.advisorPetris, Michael J.eng
dc.contributor.authorFulcher, Yan G., 1978-eng
dc.date.issued2008eng
dc.date.submitted2008 Springeng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from title screen of research.pdf file (viewed on June 19, 2009)eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2008.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Nutrition area program.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] 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.eng
dc.identifier.merlinb69061816eng
dc.identifier.oclc403807311eng
dc.identifier.urihttps://hdl.handle.net/10355/6048
dc.identifier.urihttps://doi.org/10.32469/10355/6048eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campus of the University of Missouri--Columbia.eng
dc.subject.lcshCopper in the bodyeng
dc.subject.lcshCisplatineng
dc.subject.lcshCell physiologyeng
dc.subject.lcshHuman body -- Nutritioneng
dc.titleFunctional studies of hCTR1, a high affinity human copper and cisplatin transportereng
dc.typeThesiseng
thesis.degree.disciplineNutrition area program (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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