Date Published: December 08, 2018
Publisher: Impact Journals
Author(s): Piervito Lopriore, Nazzareno Capitanio, Emanuele Panatta, Nicola Di Daniele, Alessandra Gambacurta, Gerry Melino, Ivano Amelio.
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.
p53 family is one of the most powerful families of genes due to the large spectrum of role that plays from tumour suppression, maintenance of the cellular homeostasis, contribution to development, reproduction and ageing [1–11]. As transcription factors, the three members, p53, p63 and p73, sharing high degree of structural homology, especially in their DNA-binding domains , regulate the expression of genes crucial for a wide range of cellular processes, including cell cycle arrest/apoptosis, senescence, metabolism [13–19], autophagy as well as terminal differentiation in specific cell types, such as neurons for p73 [20–22] and keratinocytes for p63 [23–27]. The functional and physical interplay within the family members is also thought to play biological roles and the interaction with the mutated forms of p53 can have implications in cancer [28–36].
20 years after the discovery of the p53 homologue, p73, we still lack a clear definition of its transcriptional signature and the extent of overlap with the ones controlled by the other p53 family members [80–82]. Here we reanalyse previously published transcriptional analysis of TAp73 depleted cells, trying to investigate potential novel transcriptional targets responsible for TAp73 function.