Role of GAC63 in transcriptional activation mediated by β-catenin

β-Catenin is a key mediator in the canonical Wnt signaling pathway, which plays important roles in multiple developmental processes. Inappropriate activation of this pathway leads to developmental defects and development of certain cancers. Upon Wnt signaling, β-catenin binds TCF/LEF transcription factors. The TCF/LEF-β-catenin complex then recruits a variety of transcriptional coactivators to the promoter/enhancer region of Wnt-responsive genes and activates target gene transcription. In this article, we demonstrate that GRIP1-associated coactivator 63 (GAC63), a recently identified nuclear receptor (NR) coactivator, interacts with β-catenin. The N-terminus of GAC63 is the binding site for β-catenin, whereas a C-terminal fragment of β-catenin including armadillo repeats 10–12 binds to GAC63. Over-expression of GAC63 enhanced the transcriptional activity of β-catenin, and also greatly enhanced TCF/LEF-regulated reporter gene activity in a β-catenin-dependent manner. Endogenous GAC63 was recruited to TCF/LEF-responsive enhancer elements when β-catenin levels were induced by LiCl. In addition, reduction of endogenous GAC63 level by small interfering RNA (siRNA) inhibited TCF/LEF-mediated gene transcription. Our findings reveal a new function of GAC63 in transcriptional activation of Wnt-responsive genes.

• Publication year

  2007

• Venue

  Nucleic Acids Research

• Publication date

  2007-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/nar/gkm095PMID 17344318PMCID 1874623
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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