A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity.

A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Research Abstract Details 

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A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Abstract Text:

Xiaoqing Mao,Byung-Eun Kim,Fudi Wang,David J Eide,Michael J Petris,

Zinc is an essential nutrient. Genetic evidence for this nutritional requirement in humans is the zinc deficiency disease, acrodermatitis enteropathica. This disorder is caused by mutations in hZIP4 (SLC39A4), a zinc importer required for zinc uptake in enterocytes and other cell types. Studies in mice have demonstrated that levels of the mZIP4 mRNA are reduced by elevated dietary zinc, resulting in a decreased abundance of the ZIP4 protein at the plasma membrane. Moreover, studies in cultured cells have demonstrated that low micromolar concentrations of zinc stimulate the endocytosis of the mZIP4 protein resulting in a reduction in cellular zinc uptake. In this study, we demonstrate an additional level of hZIP4 regulation involving ubiquitination and degradation of this transporter in elevated zinc concentrations. Mutational analysis identified a cytoplasmic histidine-rich domain that was essential for ubiquitin-dependent degradation of ZIP4 and protection against zinc toxicity. However, this motif was dispensable for zinc-induced endocytosis. These findings indicate that ubiquitin-mediated degradation of the ZIP4 protein is critical for regulating zinc homeostasis in response to the upper tier of physiological zinc concentrations, via a process that is distinct from zinc-stimulated endocytosis.

A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Publishing Authors By Initials

X Mao,BE Kim,F Wang,DJ Eide,MJ Petris,

For similar inorganic chemicals: elements: metals, heavy: zinc research abstracts see: inorganic chemicals: elements: metals, heavy: zinc research

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A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 6992-7000

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 01

YEAR: 2007

A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Keywords Mesh Terms:

KEYWORDS: Zinc

MESH TERMS: toxicity

Chemical & Substance for Abstract: A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. Information

Substance Name: Zinc

Registry Number: 7440-66-6

Grant and Affiliation Information for A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity.

AFFILIATION: Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM56285

ACRONYM: GM

MEDLINETA: J Biol Chem

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