TAp73 regulates ATP7A: possible implications for ageing-related diseases

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.

TP73-AS1 is induced by YY1 during TMZ treatment and highly expressed in the aging brain

“…Long noncoding RNA (lncRNA) are regulatory RNA molecules known to play important roles in cancer such as promoting resistance to therapy [12,13]. The lncRNA TP73-AS1 is a gene neighbor of the transcription factor (TF) p73, a member of the p53 TF family [14] known to play important roles in aging [15][16][17], cancer [18][19][20][21][22][23] and brain development [24][25][26][27] by regulating gene expression at the transcriptional and translational levels [28,29]. LncRNA function by diverse mechanisms including by regulating gene expression in cis [30] however, TP73-AS1 does not regulate p73 in GBM stem cells [31] and to best of our knowledge was not found to regulate p73 in other biological scenarios.…”