Disease relevance of Rxrb

• Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells [1].

High impact information on Rxrb

• Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis [2].
• Cloning and sequence analysis of the 5' flanking region of Coll1a2 showed that the putative 3' end of the retinoid X receptor beta gene was located 742 bp upstream of the Coll1a2 start site [3].
• Using chemical cross-linking, co-immunoprecipitation, gel mobility shift and streptavidin-biotin DNA precipitation assays, we show that H-2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3R alpha and RAR alpha) [4].
• H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes [4].
• Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene [5].

Biological context of Rxrb

• A genomic clone of mouse retinoid X receptor (RXR)-beta (Rxrb) has recently been isolated and mapped within the H2-K region of the mouse major histocompatibility complex [6].
• Rxra mapped to Chr 2 near the centromere, Rxrb mapped to the H-2 region of Chr 17, and Rxrg was tightly linked to the Pbx gene on distal Chr 1 [7].
• Ligand-dependent contribution of RXRbeta to cholesterol homeostasis in Sertoli cells [8].
• The testicular phenotypes of Cnot7(-/-) mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb) [2].
• These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences [5].

Anatomical context of Rxrb

• In contrast, like RXRbeta-null mutants, Rxrb(af20) mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux [8].
• The IR0-containing reporter was induced by RA in COS-1 cells in the presence of exogenously provided RARalpha and RXRbeta [9].
• RESULTS: Rub 125, 500, 2000 mg.kg-1.d-1 p.o. to BALB/c (or NIH) mice decreased the SLC; inhibited the phagocytosing functions of peripheral leukocytes; diminished the hemolytic activity of PFC; decreased the HC50; inhibited the DTH reaction; and showed inhibitory effects on TLT and BLT [10].
• CONCLUSION: Rub has immunosuppressive effects on immune system in mice by affecting M phi, T, and B lymphocyte, which suggests that Rub has inhibitory effects on both nonspecific and specific immune function [10].

Associations of Rxrb with chemical compounds

• Our results also indicate that RXRbeta may be activated by a ligand distinct from 9-cis retinoic acid [8].
• The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors [5].
• H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element [5].

Physical interactions of Rxrb

• However, RXR-beta binds to these elements as heterodimers with cT3R-alpha 1 and to a lesser extent with RAR-alpha [11].
• Interestingly, the simultaneous expression of the native vitamin D receptor and the retinoid X receptor beta resulted in a ligand independent transactivation of the lacZ reporter gene coupled to a mouse osteopontin vitamin D response element [12].

Other interactions of Rxrb

• A putative 250-bp promoter, which is located between Rxrb and H2-Ke4, and may possibly be their common promoter, has also been identified [6].

Analytical, diagnostic and therapeutic context of Rxrb

• Northern blot analysis revealed high levels of mRNA for the retinoid X receptor beta (RXR beta) and moderate levels of mRNAs for retinoic acid receptors alpha (RAR alpha) and gamma (RAR gamma) [13].

References