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An Acrodermatitis Enteropathica-Associated Zn Transporter, ZIP4, Regulates Human Epidermal Homeostasis

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Title
An Acrodermatitis Enteropathica-Associated Zn Transporter, ZIP4, Regulates Human Epidermal Homeostasis
Author(s)
Bin, BH; Jinhyuk Bhin; Kim, NH; Lee, SH; Jung, HS; Seo, J; Kim, DK; Daehee Hwang; Fukada, T; Lee, AY; Lee, TR; Cho, EG
Publication Date
2017-04
Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY, v.137, no.4, pp.874 - 883
Publisher
ELSEVIER SCIENCE INC
Abstract
Acrodermatitis enteropathica is an autosomal recessive disorder characterized by scaly eczematous dermatosis accompanied by alopecia and diarrhea. Various mutations in the SLC39A4 gene (ZIP4), which encodes a zinc transporter, are responsible for this disorder. However, the molecular mechanism underlying the involvement of ZIP4 in the pathogenesis of this condition has yet to be established. In this study, we report the role of ZIP4 in human epidermis. ZIP4 is predominantly expressed in human keratinocytes, and its expression is dramatically reduced on epidermal differentiation. ZIP4 knockdown in human keratinocytes down-regulates zinc (Zn) levels and the transcriptional activity of a key epidermal Zn-binding protein, DNp63, and dysregulates epidermal differentiation in a reconstituted human skin model, resulting in the appearance of proliferating keratinocytes even in the uppermost layers of the skin. We verified that, among the amino acid residues in its Zn-binding motif, Cys205 is critical for the processing and nuclear distribution of DNp63 and, therefore, Zn-dependent transcriptional activity. Our results suggest that ZIP4 is essential for maintaining human epidermal homeostasis through the regulation of Zn-dependent DNp63 activity and can provide insight into the molecular mechanisms responsible for the cutaneous symptoms observed in Acrodermatitis enteropathica patients ⓒ2016 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
URI
https://pr.ibs.re.kr/handle/8788114/3584
ISSN
0022-202X
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
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