Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1

J Biol Chem. 2006 Feb 10;281(6):3389-97. doi: 10.1074/jbc.M510403200. Epub 2005 Dec 12.


beta-Catenin, a pivotal component of the Wnt-signaling pathway, binds to and serves as a transcriptional coactivator for the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcriptional activator proteins and for the androgen receptor (AR), a nuclear receptor. Three components of the p160 nuclear receptor coactivator complex, including CARM1, p300/CBP, and GRIP1 (one of the p160 coactivators), bind to and cooperate with beta-catenin to enhance transcriptional activation by TCF/LEF and AR. Here we report that another component of the p160 nuclear receptor coactivator complex, the coiled-coil coactivator (CoCoA), directly binds to and cooperates synergistically with beta-catenin as a coactivator for AR and TCF/LEF. CoCoA uses different domains to bind GRIP1 and beta-catenin, and it uses different domains to transmit the activating signal to the transcription machinery, depending on whether it is bound to GRIP1 or beta-catenin. CoCoA associated specifically with the promoters of transiently transfected and endogenous target genes of TCF/LEF, and reduction of the endogenous CoCoA level decreased the ability of TCF/LEF and beta-catenin to activate transcription of transient and endogenous target genes. Thus, CoCoA uses different combinations of functional domains to serve as a physiologically relevant component of the Wnt/beta-catenin signaling pathway and the androgen signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calcium-Binding Proteins
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Chickens
  • Chlorocebus aethiops
  • Chromatin Immunoprecipitation
  • Enhancer Elements, Genetic
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoprecipitation
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Models, Biological
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • RNA Interference
  • Signal Transduction
  • TCF Transcription Factors / metabolism
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • beta Catenin / metabolism
  • beta Catenin / physiology*


  • CALCOCO1 protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • GRIP1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Nerve Tissue Proteins
  • TCF Transcription Factors
  • Transcription Factors
  • beta Catenin
  • Glutathione Transferase