Inhibition of Mdm2 ubiquitin-ligase activity by PRDX1 leads to the activation of p53 tumor suppressor

Mouse double minute 2 homolog (Mdm2) plays an essential role in repressing the p53 tumor suppressor. The regulation of the Mdm2-p53 signaling pathway is significant in anti-cancer therapy. The objective of this study is to determine the binding between Peroxiredoxin 1 (PRDX 1) and the Mdm2 ring finger domain as well as the functional role of PRDX1 in the p53 activation signaling pathway. PRDX1-knockdown cells are generated by lentivirus RNA interference. With the co-immunoprecipitation and GST fusion protein assay, we report that PRDX1 can interact with the ring finger domain of Mdm2, leading to the inhibition of Mdm2 ubiquitin-ligase activity. The inhibitory effect of PRDX1 on Mdm2 shows clearly in PRDX1-knockdown cells, with decreased signaling of p53 expression shown by luciferase assay. These results suggest that PRDX1 can negatively regulate the Mdm2-p53 signaling pathway, which further leads to the pro-apoptosis of cells.