Mechanism On β-catenin/Lef1 Mediated P53 Gene Expression

Canonical Wnt//β-catenin/TCF signaling pathway is one of the main signaling pathways involved in regulating cell proliferation, differentiation, apoptosis, body immunity, and other physiological and pathological processes. What is the relationship betweenβ-catenin/Lefl and p53? Previous experiments proved that p53 could downregulate and inhibite Wnt/β-catenin signaling pathway in a wide variety of tumor cells. However, it is still unkown whether Wnt/β-catenin signaling pathway could inversely regulate p53.Addrerssing to this problem, in this study, overexpressing β-catenin/Lefl in AGS cells leaded to p53 increasement at protein level. This revealed existence of negative feedback loop between β-catenin/Lefl and p53, namely β-catenin/Lefl upregulating p53, and subsequently p53 downregulating β-catenin/Lefl. In order to demonstrate whether Wnt/β-catenin/Lefl can directly regulate p53 gene transcription through protein-DNA interaction at upstream cis elements of p53 gene, by using luciferase report gene method combining with Western Blot and fluorescence quantitative PCR method, we verifiedβ-catenin/Lefl cannot directly regulate p53 gene transcription. These results hint thatβ-catenin/Lefl might regulate p53 protein level through a complex protein-protein interaction. Our results would provide solid basis for further study.