Heterodimerization with RXR

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

Farnesoid X receptor (FXR) and liver X receptors (LXRs) belong to the same NR family as PXR and CAR. Their primary role lies in cholesterol and bile acid metabolism regulation. Like many NRs of this family, FXR heterodimerizes with RXR in vivo [46]. 

Figure 8.3. A model of CAR-mediated induction of CYP2B expression by PB. Inactive CAR normally resides in the cytoplasm. PB acts on unknown cellular targets to induce the nuclear accumulation of CAR. In the nucleus, activated CAR heterodimerizes with RXR to bind response elements in the promoter of CYP2B and other target genes to induce gene expression. Phosphorylation events are thought to be important in regulating the CAR signaling pathway. Inset In the absence of PB and other CAR activators, inverse agonists can bind CAR and repress its transcriptional activity.

In contrast to the steroid receptor family, members of the thyroid receptor family typically do not associate with accessory proteins and are not localized to the extranucleus matrix. Rather, these receptors exist in the basal state associated with chromatin in the cell nucleus. When bound by hormone ligand, thyroid receptor family members dissociate from the chromatin and typically form heterodimeric combinations with the retinoid-X receptor (RXR). RXR also is capable of homodimerization in association with its ligand 9-cis retinoic acid. Thus high 9-cis retinoic acid levels apparently promote homodimerization, and low levels are permissive of heterodimerization of RXR with activation by the partner ligand. 

Vitamin A has a very important role in regulating the actions of other hormone- and nutrient-dependent genes because the RXRs can interact with other nuclear receptors to form heterodimers that are able to bind and regulate hormone and nutrient responsiveness. The RXRs are able to heterodimerize with the vitamin D receptor, the thyroid hormone receptors, the peroxisome proliferator activated... 

USP and its mammalian homolog RXR shares the ability to heterodimerize with NRs of type II, such as the vertebrate TR, RAR, VDR, PPAR [ll]and the insect EcR. For insects, in addition to EcR, USP was shown to form an heterodimeric complex with DHR38 [13], However unlike its vertebrate homolog for which ligands are known, such as the terpene 9-cis retinoic acid (9-cis RA) or the docosahexaenoic acid (DHA) [14], no hormone ligand has been identified for USP up to now. Based on the chemical analogy... 

As described above, RXR heterodimerizes with several other members of the nuclear receptors family. This implies that RXR, through these diverse, heterodimeric interactions, may regulate the expression of a very large number of genes. However, RXR does not seem to be competent to active transcription in the context of VDR-RXR, TR-RXR, or RAR-RXR complexes bound to DR3-, DR4-, or DR5-type response elements, respectively (135,233). In the case of RAR-RXR complexes (234, 235) and probably also TR-RXR com-... 

PPAR and LXR bind, upon heterodimerization with retinoid X receptor (RXR), to spe-... 

A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes and Development, 9, 769-782. 

Steroid and nuclear receptors are differentiated by their mode of DNA binding. GR, PR, AR, and ER all bind as homodimers to inverted-repeat sequences separated by three nucleotides (nnn), although the ER DNA binding domain recognizes a DNA sequence that is shared by the nuclear receptors. Nuclear receptors bind predominantly as heterodimers with RXR to direct-repeat sequences separated by one to five nucleotides. Structural studies have shown that RXR binds to the 50 half-site of the response element, which may be important for ligand-dependent transcriptional regulatory activity of the heterodimeric... 

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