The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14.
Nutrients
; 9(12)2017 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-29292794
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.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteína Supressora de Tumor p53
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Proteínas de Transporte de Cátions
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article