The molecular basis of vitamin D receptor and beta-catenin crossregulation.

Salimuddin Shah , Md Naimul Islam , Sivanesan Dakshanamurthy , Imran Rizvi , Mahadev Rao , Roger Herrell , Glendon Zinser , Meggan Valrance , Ana Aranda , Dino Moras (1) , Anthony Norman , Joellen Welsh , Stephen W Byers

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

The signaling/oncogenic activity of beta-catenin can be repressed by activation of the vitamin D receptor (VDR). Conversely, high levels of beta-catenin can potentiate the transcriptional activity of 1,25-dihydroxyvitamin D3 (1,25D). We show here that the effects of beta-catenin on VDR activity are due to interaction between the activator function-2 (AF-2) domain of the VDR and C terminus of beta-catenin. Acetylation of the beta-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 beta-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 beta-catenin, which suggests that these and perhaps other ligands would permit those functions of the VDR that involve beta-catenin interaction.

Domaines: Biologie moléculaire

Salimuddin Shah, Md Naimul Islam, Sivanesan Dakshanamurthy, Imran Rizvi, Mahadev Rao, et al.. The molecular basis of vitamin D receptor and beta-catenin crossregulation.. Molecular Cell, 2006, 21 (6), pp.799-809. ⟨10.1016/j.molcel.2006.01.037⟩. ⟨hal-00188140⟩