The molecular basis of vitamin D receptor and β-catenin crossregulation

Salimuddin Shah, Md Naimul Islam, Sivanesan Dakshanamurthy, Imran Rizvi, Mahadev Rao, Roger Herrell, Glendon Zinser, Meggan Valrance, Ana Aranda, Dino Moras, Anthony Norman, Jo Ellen Welsh, Stephen W. Byers

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203 Citations (Scopus)

Abstract

The signaling/oncogenic activity of β-catenin can be repressed by activation of the vitamin D receptor (VDR). Conversely, high levels of β-catenin can potentiate the transcriptional activity of 1,25-dihydroxyvitamin D3 (1,25D). We show here that the effects of β-catenin on VDR activity are due to interaction between the activator function-2 (AF-2) domain of the VDR and C terminus of β-catenin. Acetylation of the β-catenin C terminus differentially regulates its ability to activate TCF or VDR-regulated promoters. Mutation of a specific residue in the AF-2 domain, which renders the VDR trancriptionally inactive in the context of classical coactivators, still allows interaction with β-catenin and ligand-dependent activation of VDRE-containing promoters. VDR antagonists, which block the VDRE-directed activity of the VDR and recruitment of classical coactivators, do allow VDR to interact with β-catenin, which suggests that these and perhaps other ligands would permit those functions of the VDR that involve β-catenin interaction.

Original languageEnglish
Pages (from-to)799-809
Number of pages11
JournalMolecular Cell
Volume21
Issue number6
DOIs
Publication statusPublished - 17-03-2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Shah, S., Islam, M. N., Dakshanamurthy, S., Rizvi, I., Rao, M., Herrell, R., Zinser, G., Valrance, M., Aranda, A., Moras, D., Norman, A., Welsh, J. E., & Byers, S. W. (2006). The molecular basis of vitamin D receptor and β-catenin crossregulation. Molecular Cell, 21(6), 799-809. https://doi.org/10.1016/j.molcel.2006.01.037