L7 protein is a coregulator of vitamin D receptor-retinoid X receptor-mediated transactivation

✍ Scribed by Yvonne Berghöfer-Hochheimer; Christian Zurek; Stefan Wölfl; Peter Hemmerich; Thomas Munder

• Book ID: 101262821
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 190 KB
• Volume: 69
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19980401)69:1<1::aid-jcb1>3.0.co;2-x

✦ Synopsis

The vitamin D receptor (VDR) heterodimerizes with the retinoid X receptor (RXR) and requires additional protein-protein interactions to regulate the expression of target genes. Using the yeast two-hybrid system, we identified the previously described protein L7, that specifically interacted with the VDR in the presence of vitamin D. Deletion analysis indicated, that the N-terminus of L7, which harbours a basic region leucine zipper like domain, mediated interaction with the VDR. Binding assays with purified GST-L7 demonstrated, that L7 specifically pulled down the VDR, that was either expressed in yeast or endogenously contained in the cell line U937. Interestingly, L7 inhibited ligand-dependent VDR-RXR heterodimerization, when constitutively expressed in yeast. We also demonstrate that L7 repressed binding of VDR-RXR heterodimers to a vitamin D response element. Surprisingly, L7 recruited RXR to the same response element in the presence of 9-cis retinoic acid. Ligand-dependent protein-protein interaction in the yeast two-hybrid system confirmed, that binding of L7 also was targeted at the RXR. Our data suggest, that protein L7 is a coregulator of VDR-RXR mediated transactivation of genes, that modulates transcriptional activity by interfering with binding of the receptors to genomic enhancer elements.