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Open AccessArticle

The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14

Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA
Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL 32611, USA
Authors to whom correspondence should be addressed.
Nutrients 2017, 9(12), 1335;
Received: 8 October 2017 / Revised: 29 November 2017 / Accepted: 4 December 2017 / Published: 8 December 2017
Loss of p53’s proper function accounts for over half of identified human cancers. We identified the metal transporter ZIP14 (Zinc-regulated transporter (ZRT) and Iron-regulated transporter (IRT)-like Protein 14) as a p53-regulated protein. ZIP14 protein levels were upregulated by lack of p53 and downregulated by increased p53 expression. This regulation did not fully depend on the changes in ZIP14’s mRNA expression. Co-precipitation studies indicated that p53 interacts with ZIP14 and increases its ubiquitination and degradation. Moreover, knockdown of p53 resulted in higher non-transferrin-bound iron uptake, which was mediated by increased ZIP14 levels. Our study highlights a role for p53 in regulating nutrient metabolism and provides insight into how iron and possibly other metals such as zinc and manganese could be regulated in p53-inactivated tumor cells. View Full-Text
Keywords: ZIP14; p53; tumor suppressor; iron ZIP14; p53; tumor suppressor; iron
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Zhao, N.; Zhang, A.-S.; Wortham, A.M.; Jue, S.; Knutson, M.D.; Enns, C.A. The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14. Nutrients 2017, 9, 1335.

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