WNT/β-catenin signaling inhibits CBP-mediated RelA acetylation and expression of proinflammatory NF-κB target genes.

ABSTRACT The discovery of functional crosstalk between WNT and nuclear factor κB (NF-κB) signaling has established a more complex role for these two pathways in inflammation and cancer. However, the molecular mechanisms of the crosstalk and its biological consequences are largely unknown. Here, we show that WNT/β-catenin signaling selectively inhibits the expression of a proinflammatory subset of IL-1β-induced NF-κB target genes. WNT/β-catenin signaling does not affect nuclear translocation of the RelA subunit of NF-κB or its association with CBP (also known as CREBBP), but reduces CBP-mediated acetylation and chromatin recruitment of RelA. Thus, β-catenin selectively regulates NF-κB gene expression through its negative effects on RelA acetylation. This anti-inflammatory effect may be relevant for cancer treatment.