Repression of Wnt/β-catenin response elements by p63 (TP63).

ABSTRACTSubmitted: TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is expressed in keratinocyte stem cells and well-differentiated squamous cell carcinomas to maintain cellular potential for growth and differentiation. Controversially, activation of the Wnt/β-catenin signaling by p63 (Patturajan M. et al., 2002, Cancer Cells) and inhibition of the target gene expression (Drewelus I. et al., 2010, Cell Cycle) have been reported. Upon p63 RNA-silencing in squamous cell carcinoma (SCC) lines, a few Wnt target gene expression substantially increased, while several target genes moderately decreased. Although ΔNp63α, the most abundant isoform of p63, appeared to interact with protein phosphatase PP2A, neither GSK-3β phosphorylation nor β-catenin nuclear localization was altered by the loss of p63. As reported earlier, ΔNp63α enhanced β-catenin-dependent luc gene expression from pGL3-OT having 3 artificial Wnt response elements (WREs). However, this activation was detectable only in HEK293 c...