retinoid x receptor alpha

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..target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis...

..The PPAR-gamma LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties...

The retinoid X receptor alpha (RXRalpha) plays a central role in the regulation of many intracellular receptor signaling pathways and can mediate ligand-dependent transcription by forming homodimers or heterodimers with other nuclear ..

..subunit mRNA and protein within a few hours through activation of the thyroid hormone receptor beta retinoid X receptor alpha heterodimer because knockdown of each of the partners abrogated the stimulation by T(3)...

..esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice...

Hepatocyte retinoid X receptor alpha (RXRalpha)-deficient mice are more sensitive to ethanol toxicity than wild-type mice...

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As the obligate heterodimer partner to class II nuclear receptors, the retinoid X receptor alpha (RXRalpha) plays a vital physiological role in the regulation of multiple hepatic functions, including bile formation, intermediary ..

b>Retinoid X receptor alpha (RXRalpha), functioning as either a homodimer or a heterodimer with peroxisome proliferator receptors, is known to be involved in manifesting antiproliferative effects in cells...

The retinoid X receptor alpha (RXRalpha) is a member of the nuclear receptor superfamily that regulates transcription of target genes through heterodimerization with several partners, including peroxisome proliferator-activated receptor, ..

..Taken together, these results show that RXR binds PUFAs in solution and that these compounds induce receptor activation, suggesting that RXR could function as a fatty acid receptor in vivo...

..In this study we show that adenoviral coexpression of PPARalpha and retinoid X receptor alpha (RXRalpha) in INS-1E beta-cells synergistically and in a dose- and ligand-dependent manner increases the ..

We examined the effects of 9-cis retinoic acid (RA) on the expression levels of retinoid X receptor alpha (RXR alpha) and its phosphorylated form (p-RXR alpha) in HL-60 and HL-60R cells...

..b>Retinoid X receptor alpha (RXRalpha) mRNA and retinoic acid receptor alpha (RARalpha) mRNA levels in the small intestine showed ..

..This report reveals a potential novel strategy to enhance the detoxification of APAP or other xenobiotics by manipulating Gst activity through RXRalpha-mediated pathways...

..This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity genes can influence adaptive cytokine responses to rubella vaccination...

..In conclusion, the inhibition of RXRalpha phosphorylation and the restoration of its original function as a master regulator of nuclear receptors might therefore be an effective strategy for controlling cancer cell growth...

..Together, our results reveal a novel nongenotropic function of RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic pathway [corrected]..

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..In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and ..

..In our study, we analyzed the expression of retinoid X receptor-alpha (RXR-alpha) and its prognostic value in renal-cell carcinoma (RCC) patients exhibiting stage IV disease upon first diagnosis or thereafter...

..These new findings indicate that low doses of PPARgamma/RXRalpha ligands could be used as a new type of adjuvant to stimulate Ab production...

..There is substantial overlap in retinol and alcohol metabolism. Mice that lack retinoic acid (RA) receptor retinoid X receptor alpha (RXRalpha) expression in the liver are more susceptible to alcoholic liver disease...

..We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays...

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..Thus, in adipocytes, RXRalpha is essential for lipogenesis, but RXRgamma can functionally replace RXRalpha for the adipocyte vital functions exerted by PPARgamma/RXR heterodimers...

..In summary, our data suggest that CAR plays a role in the regulation of intestinal MDR1 expression...

..Message levels of PPARgamma and retinoid X receptor alpha (RXRalpha) in the individual cell lines were quantitated by real time-polymerase chain reaction (RT-PCR)...

..Moreover, identifying the transcript variations in different qualities and expression of RXRG at these stages is a novel input to the pre-implantation-stage knowledge...

..These structural observations provide a molecular framework for understanding the atypical transcriptional activation properties of CAR...

The X-ray crystal structure of the human constitutive androstane receptor (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds light on the mechanism of ligand-independent activation of transcription by nuclear ..

..These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics...

..This unique nongenotropic nuclear pathway supports an emerging role for IGFBP-3 as a novel, multicompartmental signaling molecule involved in induction of apoptosis in malignant cells...

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..In this study the effects of p-RXR alpha on the ability of RXR alpha and PPAR gamma ligands to inhibit growth in colon cancer cells was examined...

..4 kDa), and strict dependence on AF-2 for interaction distinguish COPR1 and COPR2 from the SMRT/NCoR type of corepressor and may represent a means of control that dampens rather than completely represses NR-mediated gene expression...

..We found the coactivator TIF2 greatly enhances binding of T3-occupied TRs to a subset of TREs, suggesting TRs may activate transcription from these TREs in an RXR-independent manner...

..Both retinoic acid receptor alpha (RARA) and retinoid X receptor alpha (RXRA) were readily detected by immunoblotting in isolated placental endothelial cells...

..Such mutants will be valuable tools in the genetic analysis of NR function...

..These results demonstrate that CAR3, unlike CAR1, is a ligand-activated receptor and that CAR3 may regulate gene expression in vivo in a manner distinct from the reference form of the receptor...

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..Furthermore, the gender- and age-dependent pattern of basal PXR and RXRalpha expression is similar to the 3 CYP3As analysed...

..Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in ..

..It is suggested that CAPE possesses the potential to enhance the efficiency of ATRA in the differentiation therapy of APL...

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..This defect leads to enhanced ileal bile salt uptake and impaired canalicular bile salt secretion by BSEP. In PFIC1, an increased load of bile acids is retained in the liver leading to cholestasis and progressive liver injury...

..Taken together, these results suggest that the unique Trp-Zip-mediated PXR homodimer plays a role in the function of this nuclear xenobiotic receptor...

..In conclusion, we found that CYP2A6 is induced via PXR and PGC-1alpha through the DR4-like element at the distal response region. This is the first study to report the molecular mechanism of the induction of CYP2A6...

..We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases...

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..Developmental or chronic lifetime exposure to organotins may therefore act as a chemical stressor for obesity and related disorders...

..Taken together these results suggest that the RXRalpha LBD exists as a dynamic ensemble of conformations, even after binding its cognate ligand. Such dynamic characteristics may allow RXRalpha to partner with multiple nuclear receptors...

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..Previous promoter analysis revealed that liver X receptor alpha (LXRalpha)/retinoid X receptor alpha (RXRalpha) complex was required for SREBP-1c gene expression in cell culture...

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..beta-Carotene cleavage in the RPE may be an alternative pathway that would ensure the retinoid supply of photoreceptor cells...

..Taken together, these data demonstrate the differential roles of NF-kappaB p65 and RARalpha/RXRalpha, interacting with the same sequence in the promoter of the human GnRH II gene to influence gene expression in a cell-specific manner...

..EMSA experiments showed VPA-mediated augmentation of CAR/retinoid X receptor alpha heterodimer binding to direct repeat 3 (DR3) and DR4 responsive elements of CYP3A4 and MDR1 genes, ..

..that tumor necrosis factor (TNF) and interleukin 1 (IL-1), but not IL-6, decrease the expression of retinoid X receptor alpha (RXRalpha), peroxisome proliferator-activated receptor alpha (PPARalpha), PPARgamma, liver X receptor ..

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..These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss...

..Interestingly, we note that all of these peptides also interact in an agonist-dependent manner with retinoid X receptor alpha (RXRalpha), suggesting that these two receptors may compete for limiting cofactors within target cells...

..These findings provide the first evidence for direct regulation of lipogenesis by bile acids and also provide a mechanistic rationale for previously unexplained observations regarding bile acid control of FAS expression...

..This resulted in a reduction in the DNA binding activity of RARalpha/retinoid X receptor alpha (RXRalpha) heterodimer, the separation of RXRalpha from RARalpha and the translocation of RXRalpha from ..

..The hypothesis that the difference in binding site polarity might be exploited to build RXR-selective ligands is tested with some compounds having a thiazolidinedione anchoring group...

..These data identify Rev-erbalpha as a new LXR target gene, inhibiting LXR-induction of TLR-4 in a negative transcriptional feedback loop, but not cholesterol homeostasis gene expression...

..Taken together, our present findings indicate that ERAP140/Nbla10993 plays an important role in the regulation of ATRA-mediated neuronal differentiation, and is a novel member of prognostic indicators for neuroblastoma...

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..Taken together, these results suggest the role of mitochondrial-mediated pathway and ER stress as a key event in 4-HPR-induced apoptosis in glioma cells...

..receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXRalpha)...

..We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers...

..This result suggests that 9cRA-bound RXRalpha can affect the PPARgamma AF-2 helix in solution and demonstrates that NMR is a powerful new tool for studying the mechanism of allosteric ligand activation in RXR heterodimers...

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..Our data suggest that in healthy elderly men reduction of RXRbeta expression in PBMCs might be a common feature of physiological senescence...

..Transcriptional activation of the SHP (small heterodimer partner) gene by the FXR-RXRalpha (retinoid X receptor alpha) heterodimer was also enhanced by PGC-1alpha in the presence of CDCA (chenodeoxycholic acid)...

..The addition of RARE activity to previously described functions of the 5'-distal enhanceosome underscores the importance of this region as a key integration point for regulatory control of PDGF-A expression...

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..Finally, we show that the RA-responsive promoter region is also able to induce expression of a reporter gene in extraembryonic endoderm of 7.5 day-old transgenic mouse embryos...

..Our results raise the interesting possibility that a RXR-specific ligand may modulate T3-mediated signaling by inducing additional interactions between TRE-bound TR-RXR heterodimer and the coactivator...

..alpha (RARalpha), retinoic acid receptor beta (RARbeta), retinoic acid receptor gamma (RARgamma), retinoid X receptor alpha (RXRalpha), retinoid X receptor beta (RXRbeta), retinaldehyde dehydrogenase-2 (RALDH-2), and peroxisome ..

..glucose-regulated protein (HSPA5), valyl-tRNA synthetase 1 (VARS1), complement component V (C5), PBX3, retinoid X receptor alpha (RXRA), ORFX/RING3L, and others...

..This indicates that the peptide-producing magnocellular neurons of the SON express a specific set of transcription factors of the nuclear hormone receptor family...

..that the thyroid hormone receptor alpha (TR alpha) formed a heterodimeric complex, with either the retinoid X receptor alpha or gamma 1 isoforms (RXR alpha, RXR gamm), on the MyoD TRE that was specifically competed by other well ..

..These results reveal the existence of functional cross talk between the GR and PXR, and may explain some controversial aspects of the role of the GR in CYP3A4 induction...

..fragment of mouse PC gene linked to a luciferase reporter construct and with plasmids overexpressing retinoid X receptor alpha/PPARgamma1 or retinoid X receptor alpha/PPARgamma2 showed a 6-8-fold increase above the basal promoter ..

..The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed...

..In Chinese hamster ovary cells transfected with retinoid X receptor alpha (RXRalpha)/FXR, only chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were able to stimulate a ..

..In particular, there is evidence suggesting that the activation of peroxisome proliferator-activated receptors (PPARs) is an important factor in the regulation of sebocyte lipogenesis...

..Here, we also show that alterations in SREBP expression play a role in mediating cell type-dependent differences in T3 regulation of ACCalpha transcription...

..The dTAFII110 did not bind to human retinoid X receptor alpha in vitro, indicating that this TAF interacts differentially with nuclear receptors...

..Binding to COUP-TF2 was specific because FOG-2 did not interact with the ligand-binding domains of retinoid X receptor alpha, glucocorticoid receptor, and peroxisome proliferating antigen receptor gamma, which are related to the ..

..The mutant proteins were tested for their ability to form v-ErbA homodimers and heterodimers with retinoid X receptor alpha on differently oriented core motifs by electrophoretic mobility shift assay...

..The aim of the present study was to evaluate the clinical significance of PPAR-gamma and RXR-alpha expression in pancreatic adenocarcinoma...

..A-II) promoter contains a thyroid HRE (hormone response element), which strongly binds RXRalpha (retinoid X receptor alpha)/T(3)Rbeta (thyroid receptor beta) heterodimers and weakly T(3)Rbeta homodimers, but does not bind other ..

..of action of retinoids in the context of the prostate, we used the Cre-loxP system to disrupt the retinoid X receptor alpha (RXRalpha) gene specifically in the prostatic epithelium of the mouse...

..The reasons for such dysregulation remain to be determined; however, the data are consistent with the hypothesis that PPARs may play a role in preterm labor and infection-complicated preterm deliveries...

..To observe the preventive and therapeutic effects of L-carnitine on the metabolic disorder and cardiac remodeling in alcoholic cardiomyopathy...

..This increase in transcription requires the binding of retinoid X receptor alpha (RXRalpha)-FXRalpha heterodimers to a novel inverted repeat with one nucleotide spacing (IR-1) present ..

b>Retinoid x receptor alpha (RXRalpha) serves as an active partner of peroxisome proliferator-activated receptor (PPARalpha)...

..to define the role of p53 in pharmacological differentiation therapies that target nuclear receptors Retinoid X Receptor alpha (RXRalpha) and Peroxisome proliferator-activated receptor gamma (PPARgamma)...

..to define the role of p53 in pharmacological differentiation therapies that target nuclear receptors Retinoid X Receptor alpha (RXRalpha) and Peroxisome proliferator-activated receptor gamma (PPARgamma)...

..catagen stage of the normal hair cycle, including hairless (hr), the vitamin D receptor (VDR), and the retinoid X receptor alpha (RXRalpha) have been identified on the basis of mutations in these genes which cause hair loss ..

..In general the work proposed tests the molecular mechanisms, and significance of, cross regulation of beta-catenin/TCF retinoid signaling pathways. ..

..We have documented that the retinoid X receptor alpha null (RXRalpha-/-) mouse is an excellent model system to aid our understanding of how retinoic acid ..

..of differentiation regulators including retinoblastoma tumor suppressor protein (pRb), RARalpha, and retinoid X receptor alpha (RXRalpha)...

..Finally, these studies will provide a basis for screening of individuals with polymorphisms in TLR genes during clinical trials of new drugs. ..

..Our concept protocols propose to examine networks of co-expressed genes in the uterus during preterm birth. We accept the RFA's capitation and participatory stipulations and stand ready to contribute as a member of the Network. ..

..The results of this study could also potentially provide a basis for clinical trials using TRAIL or analogues against gliomas and allow rational selection of agents to modulate the tumor resistance to TRAIL. ..

..It will utilize comprehensive promoter-reporter transfection studies, EMSA, footprinting, and overexpression studies to define the protein-DNA interactions critical to HIMF gene expression during the perinatal period. ..

..This study could contribute to understanding the mechanisms of metabolic diseases caused by dysregulation of bile acid synthesis and develop therapeutic agents to treat dyslipidemia, liver diseases, obesity and type II diabetes. ..

..These studies will help us understand how SHP activity is modulated and may suggest new approaches for treating metabolic diseases. ..

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..The present study involves the use of a novel melanoma mouse model to study the molecular mechanism underlying the role of skin keratinocytes to control melanocyte mitogenesis and melanomagenesis. ..

..Taken together the proposed studies will greatly enhance our knowledge of PPARalpha's mechanism of action and hence our understanding of an important class of carcinogen. ..

..The results of this study could also potentially provide a basis for clinical trials using TRAIL or analogues against gliomas and allow rational selection of agents to modulate the tumor resistance to TRAIL. ..

..It may also shed light on the pathogenesis of non-alcoholic fatty liver disease. ..

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..The present study involves the use of a novel melanoma mouse model to study the molecular mechanism underlying the role of skin keratinocytes to control melanocyte mitogenesis and melanomagenesis. ..

..Such data could be relevant not only to future trials of retinoids in gliomas but also for ongoing trials of fenretinide in other malignancies. ..

..III) To test the hypothesis that disruption of RXRalpha expression during cardiogenesis results in cardiac defects that are TGFbeta2 dependent. ..

..Taken together the proposed studies will greatly increase our knowledge of PPARalpha's mechanism of action and hence our understanding of an important class of chemical carcinogens. ..

..The long term objective of this research project is to understand molecular mechanisms of regulation of bile acid synthesis and mechanisms of human diseases in bile acid metabolism and cholesterol homeostasis. ..

..The excellent research environment at Johns Hopkins coupled with an extensive collaborative team of experts in relevant fields of study is ideal for successful completion of the proposed work. ..

..Examination of altered RNA levels in cancers and preneoplastic lesions in an animal model will facilitate the development of relevant surrogate biomarkers for cancer chemoprevention studies (one of the stated goals of this RFA). ..

..The studies may also facilitate the design of therapeutic agents for treating these metabolic disorders. ..

..In addition, receptor-selective retinoids are currently used in cancer therapy and are being evaluated for diabetes. This work will help evaluate possible side effects of these therapies. ..

..The results of this study could also potentially provide a basis for clinical trials using TRAIL or analogues against gliomas and allow rational selection of agents to modulate the tumor resistance to TRAIL. ..

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..Analytic tools will include flow cytometry, immunohistochemistry, immunofluorescence microscopy, morphometric analysis, cytokine/chemokine ELISA. ..

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..Since these pathways can be manipulated by pharmacological agents, this hypothesis suggests possible new therapies for alcoholic fatty liver and possibly steatohepatitis. ..

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