title: 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.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich 8057, Switzerland Division of Immunology, University Children's Hospital Zurich, Zurich 8032, Switzerland.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich 8057, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Fey
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich 8057, Switzerland hottiger@vetbio.uzh.ch.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051176:beta Catenin; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
keywords: Acetylation; CBP; NF-κB; WNT; β-catenin