RXRβ: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements

Difference and similarity of DNA sequence recognized by VDR homodimer and VDR/RXR heterodimer

“…Although the both VDREs of mSPP-1 and rOST had been shown to be vitamin D inducible by transient transfection assay in mammalian cells (10)(11)(12), the VDR binding to two VDREs was apparently different. It was reported that the RXR enhances binding of the VDR, the RAR and the TR to their specific DNA response elements (4,5). So, we next examined the effect of RXR on the VDR DNA binding.…”

“…In addition, it has been reported that the VDR DNA binding domain expressed in Escherichia coli can bind to the mSPP-1 VDRE, but not to other VDREs (16,17). However, the presence of RXR allows the VDR to bind various VDREs (5,(13)(14)(15)18). From these facts, we thought that the DNA binding specificity of the VDR could be altered by the heterodimer formation with the RXR.…”

“…recognize palindromic DNA sequences as homodimers. On the contrary, the VDR, the retinoic acid receptor (RAR) and the thyroid hormone receptor (TR) bind to direct repeats of 5'-PuG(G/T)TCA motif as heterodimers with the retinoid X receptor (RXR) (4,5). Based on transient transfection studies using synthetic oligonucleotides as HREs, the transactivation by the VDR-RXR, TR-RXR and RAR-RXR complexes is shown to preferentially occur through direct repeats spaced by 3, 4 and 5 nucleotides, respectively (6,7).…”

Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

“…While retinoid-dependent transactivation by RXR is mediated in part by RXR homodimers (66), RXR is also able to form heterodimers with TR and VDR (7,18,36,37,46,48,64,65). In each case, target gene binding by the nuclear hormone receptor is greatly enhanced by its partnership with RXR.…”

Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia

“…[10][11][12][13] In 1990, the family of retinoid 'X' receptors (RXRs) was described, which were shown to act as cofactors for RARs as well as receptors for vitamin D, thyroid hormone and peroxi-some proliferation-associated proteins. [14][15][16][17] Whereas all-trans RA binds only RARs, 9-cis RA binds and activates both RARs and RXRs. [18][19][20] Preclinical studies also showed that 9-cis RA was more potent than all-trans RA in inducing myeloid differentiation in HL60 cells.…”