The p53 Protein is a Suppressor of Atox1 Copper Chaperon in Tumor Cells Under Genotoxic Effects

Abstract

The p53 protein is crucial for regulating cell survival and apoptosis in response to DNA damage. However, its influence on therapy effectiveness is controversial: when DNA damage is high p53 directs cells toward apoptosis, while under moderate genotoxic stress it saves the cells from death and promote DNA repair. Furthermore, these processes are influenced by the metabolism of transition metals, particularly copper since they serve as cofactors for critical enzymes. The metallochaperone Atox1 is under intensive study in this context because it serves as transcription factor allegedly mediating described effects of copper. Investigating the interaction between p53 and Atox1 could provide insights into tumor cell survival and potential therapeutic applications in oncology. This study explores the relationship between p53 and Atox1 in HCT116 and A549 cell lines with wild type and knockout TP53. The study found an inverse correlation between Atox1 and p53 at the transcriptional and translational levels in response to genotoxic stress. Atox1 expression decreased with increased p53 activity, while cells with inactive p53 had significantly higher levels of Atox1. Suppression of both genes increased apoptosis, while suppression of the ATOX1 gene prevented apoptosis even under the treatment with chemotherapeutic drugs. The findings suggest that Atox1 may act as one of key elements in promotion of cell cycle under DNA-damaging conditions, while p53 works as an antagonist by inhibiting Atox1. Understanding of this relationship could help identify potential targets in cell signaling pathways to enhance the effectiveness of antitumor therapy, especially in tumors with mutant or inactive p53.