The tumor suppressor, P53, decreases the metal transporter, ZIP14

Ningning Zhao, An Sheng Zhang, Aaron M. Wortham, Shall Jue, Mitchell D. Knutson, Caroline A. Enns

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1335
JournalNutrients
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2017

Keywords

  • Iron
  • P53
  • Tumor suppressor
  • ZIP14

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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