Y. Berghoferhochheimer et al., L7 PROTEIN IS A COREGULATOR OF VITAMIN-D-RECEPTOR RETINOID-X RECEPTOR-MEDIATED TRANSACTIVATION, Journal of cellular biochemistry, 69(1), 1998, pp. 1-12
The vitamin D receptor (VDR) heterodimerizes with the retinoid X recep
tor (RXR) and requires additional protein-protein interactions to regu
late 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 analys
is indicated, that the N-terminus of L7, which harbours a basic region
leucine zipper like domain, mediated interaction with the VDR. Bindin
g assays with purified GST-L7 demonstrated, that L7 specifically pulle
d down the VDR, that was either expressed in yeast or endogenously con
tained in the cell line U937. Interestingly, L7 inhibited ligand-depen
dent VDR-RXR heterodimerization, when constitutively expressed in yeas
t. We also demonstrate that L7 repressed binding of VDR-RXR heterodime
rs to a vitamin D response element. Surprisingly, L7 recruited RXR to
the same response element in the presence of 9-cis retinoic acid. Liga
nd-dependent protein-protein interaction in the yeast two-hybrid syste
m confirmed, that binding of L7 also was targeted at the RXR. Our data
suggest,that protein L7 is a coregulator of VDR-RXR mediated transact
ivation of genes, that modulates transcriptional activity by interferi
ng with binding of the receptors to genomic enhancer elements. (C) 199
8 Wiley-Liss, Inc.