dc.contributor.advisor | Petris, Michael J. | eng |
dc.contributor.author | Mao, Xiaoqing, 1972- | eng |
dc.date.issued | 2007 | eng |
dc.date.submitted | 2007 Summer | eng |
dc.description | The 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.description | Title from title screen of research.pdf file (viewed on January 3, 2008) | eng |
dc.description | Thesis (Ph. D.) University of Missouri-Columbia 2007. | eng |
dc.description.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. | eng |
dc.description.bibref | Includes bibliographical references. | eng |
dc.identifier.merlin | b61727015 | eng |
dc.identifier.oclc | 186990087 | eng |
dc.identifier.uri | https://doi.org/10.32469/10355/6023 | eng |
dc.identifier.uri | https://hdl.handle.net/10355/6023 | |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | Access is limited to the campuses of the University of Missouri. | eng |
dc.source | Submitted by University of Missouri--Columbia Graduate School. | eng |
dc.subject | acrodermatitis enteropathica. | eng |
dc.subject | acrodermatitis enteropathica | eng |
dc.subject.lcsh | Zinc deficiency diseases | eng |
dc.subject.lcsh | Zinc in the body | eng |
dc.subject.lcsh | Homeostasis | eng |
dc.subject.lcsh | Proteins | eng |
dc.subject.lcsh | Ubiquitin | eng |
dc.title | Molecular and cell biological studies of mammalian zinc transporters | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Biochemistry (Agriculture) (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph. D. | eng |