A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1.

In addition to its role as a 9-cis retinoic acid receptor, RXR has an important role in the regulation of multiple hormonal pathways through heterodimerization with nuclear receptors. Here, we show that two orphan receptors, NGFI-B and NURR1, which have been shown previously to interact with DNA as monomers, also ...
can heterodimerize with RXR. These heterodimers bind selectively to a class of retinoic acid response elements composed of direct repeats spaced by 5 nucleotides. In this respect they are similar to heterodimers formed between RXR and the receptor for all-trans retinoic acid, RAR. However, whereas RXR is inhibited in the RXR-RAR heterodimer, NGFI-B/NURR1 promote efficient activation in response to RXR ligands and therefore shift RXR from a silent to an active heterodimerization partner. These data show that NGFI-B and NURR1 can increase the potential of RXR to modulate gene expression in a ligand-dependent manner by allowing a distinct class of direct repeats to serve as specific RXR response elements. Because expression of both NGFI-B and NURR1 is rapidly induced by various growth factors, these findings also suggest a novel mechanism for convergence between vitamin A or retinoid and growth factor signaling pathways.
Mesh Terms:
Base Sequence, DNA, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Receptor Subfamily 4, Group A, Member 1, Nuclear Receptor Subfamily 4, Group A, Member 2, Protein Binding, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Receptors, Steroid, Repetitive Sequences, Nucleic Acid, Retinoid X Receptors, Signal Transduction, Transcription Factors, Tumor Cells, Cultured, Vitamin A
Genes Dev.
Date: Apr. 01, 1995
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