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Research Paper|Volume 10, Issue 12|pp 3745—3760

TAp73 regulates ATP7A: possible implications for ageing-related diseases

Piervito Lopriore1,2, Nazzareno Capitanio2, Emanuele Panatta1, Nicola Di Daniele3, Alessandra Gambacurta4, Gerry Melino1,4, Ivano Amelio1
  • 1MRC Toxicology Unit, University of Cambridge, Leicester LE1 7HB, United Kingdom
  • 2Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
  • 3Department of Systems Medicine, Nephrology and Hypertension Unit, Tor Vergata University Hospital, Rome, Italy
  • 4Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
Received: October 4, 2018Accepted: November 15, 2018Published: December 8, 2018
https://doi.org/10.18632/aging.101669

Copyright: © 2018 Lopriore et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The p53 family member p73 controls a wide range of cellular function. Deletion of p73 in mice results in increased tumorigenesis, infertility, neurological defects and altered immune system. Despite the extensive effort directed to define the molecular underlying mechanism of p73 function a clear definition of its transcriptional signature and the extent of overlap with the other p53 family members is still missing. Here we describe a novel TAp73 target, ATP7A a member of a large family of P-type ATPases implicated in human neurogenerative conditions and cancer chemoresistance. Modulation of TAp73 expression influences basal expression level of ATP7A in different cellular models and chromatin immunoprecipitation confirmed a physical direct binding of TAp73 on ATP7A genomic regions. Bioinformatic analysis of expression profile datasets of human lung cancer patients suggests a possible implication of TAp73/ATP7A axis in human cancer. These data provide a novel TAp73-dependent target which might have implications in ageing-related diseases such as cancer and neurodegeneration.