While the MDM2-p53 interaction has been extensively documented, MDM2 overexpression is observed in human cancers with little or no functional p53, indicating that mdm2 expression is regulated by mechanisms independent of p53. Researchers reveal NFAT1's novel role in cancer biology by demonstrating its direct regulation of MDM2 expression. NFAT1 binds to the mdm2 P2 promoter, increasing mdm2 transcription independently of p53. This leads to elevated MDM2 levels, impairing p53 function in DNA damage response. The study highlights NFAT signaling dysregulation in cancer and its association with MDM2 overexpression in hepatocellular carcinoma tissues. It suggests NFAT1 as a potential therapeutic target and prompts further research into cancer development and therapy.
Figure 1. The role of NFAT1 in mdm2 transcription regulation was investigated using Luc Reporter Cell Line-HCT116. HCT116 (p53+/+ and p53−/−) cells were transfected with the NFAT1 plasmid, and mdm2 mRNA levels were measured. Additionally, mdm2 promoter activity was assessed by co-transfecting the NFAT1 plasmid with a luciferase reporter vector, and luciferase levels were quantified. Results suggest NFAT1's involvement in mdm2 transcriptional regulation, providing insights into cellular processes. (Zhang X, et al., 2012)