Figure 4

Positive feedback loops between β-catenin and downstream targets. The β-catenin/Tcf complex directly binds to binding element site (TBE) of the AKT1 and STAT3 gene promoter. In turn AKT1 activation induces β-catenin phosphorylation at Ser552 directly or by GSK-3β phosphorylation and STAT3 activation increases the nuclear accumulation of β-catenin, thereby increasing β-catenin nuclear translocation and enhancing transcriptional activity. In addition, the E2F1 promoter activity is repressed by overexpression of β-catenin/Tcf, and E2F1 inhibites β-catenin transcription directly or via upregulation of Siah1.