Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 8 of 8

Publication Record

Connections

Structure of the heterodimeric ecdysone receptor DNA-binding complex.
Devarakonda S, Harp JM, Kim Y, Ozyhar A, Rastinejad F
(2003) EMBO J 22: 5827-40
MeSH Terms: Amino Acid Sequence, Animals, Base Sequence, Binding Sites, DNA, DNA-Binding Proteins, Dimerization, Drosophila, Drosophila Proteins, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Receptors, Steroid, Retinoid X Receptors, Static Electricity, Transcription Factors
Show Abstract · Added January 30, 2015
Ecdysteroids initiate molting and metamorphosis in insects via a heterodimeric receptor consisting of the ecdysone receptor (EcR) and ultraspiracle (USP). The EcR-USP heterodimer preferentially mediates transcription through highly degenerate pseudo-palindromic response elements, resembling inverted repeats of 5'-AGGTCA-3' separated by 1 bp (IR-1). The requirement for a heterodimeric arrangement of EcR-USP subunits to bind to a symmetric DNA is unusual within the nuclear receptor superfamily. We describe the 2.24 A structure of the EcR-USP DNA-binding domain (DBD) heterodimer bound to an idealized IR-1 element. EcR and USP use similar surfaces, and rely on the deformed minor groove of the DNA to establish protein-protein contacts. As retinoid X receptor (RXR) is the mammalian homolog of USP, we also solved the 2.60 A crystal structure of the EcR-RXR DBD heterodimer on IR-1 and found the dimerization and DNA-binding interfaces to be the same as in the EcR-USP complex. Sequence alignments indicate that the EcR-RXR heterodimer is an important model for understanding how the FXR-RXR heterodimer binds to IR-1 sites.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling.
Yoshikawa T, Ide T, Shimano H, Yahagi N, Amemiya-Kudo M, Matsuzaka T, Yatoh S, Kitamine T, Okazaki H, Tamura Y, Sekiya M, Takahashi A, Hasty AH, Sato R, Sone H, Osuga J, Ishibashi S, Yamada N
(2003) Mol Endocrinol 17: 1240-54
MeSH Terms: Animals, Anticholesteremic Agents, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, DNA-Binding Proteins, Fatty Acids, Gene Expression Regulation, Hepatocytes, Humans, Hydrocarbons, Fluorinated, Liver, Liver X Receptors, Male, Mice, Mice, Inbred C57BL, Nutritional Physiological Phenomena, Orphan Nuclear Receptors, Promoter Regions, Genetic, Pyrimidines, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Response Elements, Retinoid X Receptors, Signal Transduction, Sterol Regulatory Element Binding Protein 1, Sulfonamides, Transcription Factors
Show Abstract · Added March 27, 2013
Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.
0 Communities
1 Members
0 Resources
29 MeSH Terms
Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity.
Imai T, Jiang M, Kastner P, Chambon P, Metzger D
(2001) Proc Natl Acad Sci U S A 98: 4581-6
MeSH Terms: Animals, Cellular Senescence, Hepatectomy, Hepatocytes, Liver Regeneration, Mice, Mice, Knockout, Receptors, Retinoic Acid, Retinoid X Receptors, Transcription Factors
Show Abstract · Added February 25, 2015
Retinoid X receptors (RXRs) are involved in a number of signaling pathways as heterodimeric partners of numerous nuclear receptors. Hepatocytes express high levels of the RXRalpha isotype, as well as several of its putative heterodimeric partners. Germ-line disruption (knockout) of RXRalpha has been shown to be lethal in utero, thus precluding analysis of its function at later life stages. Hepatocyte-specific disruption of RXRalpha during liver organogenesis has recently revealed that the presence of hepatocytes is not mandatory for the mouse, at least under normal mouse facility conditions, even though a number of metabolic events are impaired [Wan, Y.-J., et al. (2000) Mol. Cell. Biol. 20, 4436-4444]. However, it is unknown whether RXRalpha plays a role in the control of hepatocyte proliferation and lifespan. Here, we report a detailed analysis of the liver of mice in which RXRalpha was selectively ablated in adult hepatocytes by using the tamoxifen-inducible chimeric Cre recombinase system. Our results show that the lifespan of adult hepatocytes lacking RXRalpha is shorter than that of their wild-type counterparts, whereas proliferative hepatocytes of regenerating liver exhibit an even shorter lifespan. These lifespan shortenings are accompanied by increased polyploidy and multinuclearity. We conclude that RXRalpha plays important cell-autonomous function(s) in the mechanism(s) involved in the lifespan of hepatocytes and liver regeneration.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter.
Yoshikawa T, Shimano H, Amemiya-Kudo M, Yahagi N, Hasty AH, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Kimura S, Ishibashi S, Yamada N
(2001) Mol Cell Biol 21: 2991-3000
MeSH Terms: Alitretinoin, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cell Line, Cholesterol, DNA-Binding Proteins, Humans, Hydroxycholesterols, Liver, Molecular Sequence Data, Promoter Regions, Genetic, Receptors, Retinoic Acid, Retinoid X Receptors, Sterol Regulatory Element Binding Protein 1, Trans-Activators, Transcription Factors, Transcription, Genetic, Tretinoin, Tumor Cells, Cultured
Show Abstract · Added March 27, 2013
In an attempt to identify transcription factors which activate sterol-regulatory element-binding protein 1c (SREBP-1c) transcription, we screened an expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse SREBP-1 gene promoter. We cloned and identified the oxysterol receptors liver X receptor (LXRalpha) and LXRbeta as strong activators of the mouse SREBP-1c promoter. In the transfection studies, expression of either LXRalpha or -beta activated the SREBP-1c promoter-luciferase gene in a dose-dependent manner. Deletion and mutation studies, as well as gel mobility shift assays, located an LXR response element complex consisting of two new LXR-binding motifs which showed high similarity to an LXR response element recently found in the ABC1 gene promoter, a reverse cholesterol transporter. Addition of an LXR ligand, 22(R)-hydroxycholesterol, increased the promoter activity. Coexpression of retinoid X receptor (RXR), a heterodimeric partner, and its ligand 9-cis-retinoic acid also synergistically activated the SREBP-1c promoter. In HepG2 cells, SREBP-1c mRNA and precursor protein levels were induced by treatment with 22(R)-hydroxycholesterol and 9-cis-retinoic acid, confirming that endogenous LXR-RXR activation can induce endogenous SREBP-1c expression. The activation of SREBP-1c by LXR is associated with a slight increase in nuclear SREBP-1c, resulting in activation of the gene for fatty acid synthase, one of its downstream genes, as measured by the luciferase assay. These data demonstrate that LXR-RXR can modify the expression of genes for lipogenic enzymes by regulating SREBP-1c expression, providing a novel link between fatty acid and cholesterol metabolism.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes.
Imai T, Jiang M, Chambon P, Metzger D
(2001) Proc Natl Acad Sci U S A 98: 224-8
MeSH Terms: Adipocytes, Adipose Tissue, Animals, Body Temperature, Body Weight, Cell Differentiation, Dimerization, Enzyme Induction, Fasting, Histocytochemistry, Hypothermia, Integrases, Lipolysis, Mice, Mice, Transgenic, Mutagenesis, Obesity, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Receptors, Estrogen, Receptors, Retinoic Acid, Recombinant Fusion Proteins, Retinoid X Receptors, Sodium Glutamate, Stem Cells, Tamoxifen, Time Factors, Transcription Factors, Viral Proteins
Show Abstract · Added February 25, 2015
Retinoid X receptor alpha (RXRalpha) is involved in multiple signaling pathways, as a heterodimeric partner of several nuclear receptors. To investigate its function in energy homeostasis, we have selectively ablated the RXRalpha gene in adipocytes of 4-week-old transgenic mice by using the tamoxifen-inducible Cre-ERT2 recombination system. Mice lacking RXRalpha in adipocytes were resistant to dietary and chemically induced obesity and impaired in fasting-induced lipolysis. Our results also indicate that RXRalpha is involved in adipocyte differentiation. Thus, our data demonstrate the feasibility of adipocyte-selective temporally controlled gene engineering and reveal a central role of RXRalpha in adipogenesis, probably as a heterodimeric partner for peroxisome proliferator-activated receptor gamma.
0 Communities
1 Members
0 Resources
29 MeSH Terms
Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death.
Guan YF, Zhang YH, Breyer RM, Davis L, Breyer MD
(1999) Neoplasia 1: 330-9
MeSH Terms: Alitretinoin, Antineoplastic Agents, Apoptosis, Carcinoma, Transitional Cell, Carrier Proteins, Cell Death, Chromans, Cyclin D1, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA, DNA, Complementary, Dose-Response Relationship, Drug, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, G1 Phase, Humans, Immunoblotting, In Situ Hybridization, Ligands, Luciferases, Myelin P2 Protein, Neoplasm Proteins, Nicotinic Acids, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Retinoid X Receptors, Ribonucleases, Tetrahydronaphthalenes, Thiazoles, Thiazolidinediones, Transcription Factors, Transcriptional Activation, Transfection, Tretinoin, Troglitazone, Tumor Cells, Cultured, Tumor Suppressor Proteins, Urinary Bladder Neoplasms
Show Abstract · Added December 21, 2013
The present study examined the expression and role of the thiazolidinedione (TZD)-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma), in human bladder cancers. In situ hybridization shows that PPARgamma mRNA is highly expressed in all human transitional epithelial cell cancers (TCCa's) studied (n=11). PPARgamma was also expressed in five TCCa cell lines as determined by RNase protection assays and immunoblot. Retinoid X receptor alpha (RXRalpha), a 9-cis-retinoic acid stimulated (9-cis-RA) heterodimeric partner of PPARgamma, was also co-expressed in all TCCa tissues and cell lines. Treatment of the T24 bladder cancer cells with the TZD PPARgamma agonist troglitazone, dramatically inhibited 3H-thymidine incorporation and induced cell death. Addition of the RXRalpha ligands, 9-cis-RA or LG100268, sensitized T24 bladder cancer cells to the lethal effect of troglitazone and two other PPAR- activators, ciglitazone and 15-deoxy-delta(12,14)-PGJ2 (15dPGJ(2)). Troglitazone treatment increased expression of two cyclin-dependent kinase inhibitors, p21(WAF1/CIP1) and p16(INK4), and reduced cyclin D1 expression, consistent with G1 arrest. Troglitazone also induced an endogenous PPARgamma target gene in T24 cells, adipocyte-type fatty acid binding protein (A-FABP), the expression of which correlates with bladder cancer differentiation. In situ hybridization shows that A-FABP expression is localized to normal uroepithelial cells as well as some TCCa's. Taken together, these results demonstrate that PPARgamma is expressed in human TCCa where it may play a role in regulating TCCa differentiation and survival, thereby providing a potential target for therapy of uroepithelial cancers.
0 Communities
1 Members
0 Resources
40 MeSH Terms
Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver.
Wan YJ, An D, Cai Y, Repa JJ, Hung-Po Chen T, Flores M, Postic C, Magnuson MA, Chen J, Chien KR, French S, Mangelsdorf DJ, Sucov HM
(2000) Mol Cell Biol 20: 4436-44
MeSH Terms: Animals, Homeostasis, Liver, Mice, Mutation, Receptors, Retinoic Acid, Retinoid X Receptors, Signal Transduction, Transcription Factors
Show Abstract · Added February 23, 2011
A large number of physiological processes in the adult liver are regulated by nuclear receptors that require heterodimerization with retinoid X receptors (RXRs). In this study, we have used cre-mediated recombination to disrupt the mouse RXRalpha gene specifically in hepatocytes. Although such mice are viable, molecular and biochemical parameters indicate that every one of the examined metabolic pathways in the liver (mediated by RXR heterodimerization with PPARalpha, CARbeta, PXR, LXR, and FXR) is compromised in the absence of RXRalpha. These data demonstrate the presence of a complex circuitry in which RXRalpha is integrated into a number of diverse physiological pathways as a common regulatory component of cholesterol, fatty acid, bile acid, steroid, and xenobiotic metabolism and homeostasis.
1 Communities
1 Members
0 Resources
9 MeSH Terms
Retinoic acid receptor- and retinoid X receptor-selective retinoids activate signaling pathways that converge on AP-1 and inhibit squamous differentiation in human bronchial epithelial cells.
Lee HY, Dawson MI, Walsh GL, Nesbitt JC, Eckert RL, Fuchs E, Hong WK, Lotan R, Kurie JM
(1996) Cell Growth Differ 7: 997-1004
MeSH Terms: Alitretinoin, Benzoates, Bexarotene, Blotting, Northern, Bronchi, Cell Differentiation, Epithelium, Humans, Isomerism, Luciferases, Receptors, Retinoic Acid, Retinoid X Receptors, Retinoids, Signal Transduction, Tetrahydronaphthalenes, Transcription Factor AP-1, Transcription Factors, Transfection, Tretinoin
Show Abstract · Added March 5, 2014
Human bronchial epithelial (HBE) cells undergo squamous differentiation in response to a variety of conditions in tissue culture, and retinoid treatment has been shown to reverse this process. Retinoids mediate their effects through the retinoic acid and retinoid X nuclear receptors (RAR and RXR, respectively), which form RAR-RXR heterodimers, RXR homodimers, and heterodimers of RXR and certain orphan receptors. These receptor dimers bind to distinct response elements, activating separate pathways. In this study, we investigated the roles of RAR and RXR signaling pathways in the inhibition of HBE squamous differentiation. After induction of squamous differentiation by confluent growth, HBE cells were treated with retinoids that selectively activate RARs (E-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthaienyl)-1- propenyl] benzoic acid), RXRs (4-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]benzoic acid), or both RARs and RXRs (9-c/s retinoic acid). These retinoids inhibited the mRNA expression of the squamous differentiation markers transglutaminase type I, involucrin, keratin 5, and keratin 13, suggesting that inhibition of HBE squamous differentiation could be mediated by activation of either RAR or RXR signaling pathways. We examined the role of AP-1 as a potential effector of these retinoid pathways. AP-1 transcriptional activity was reduced markedly by these retinoids, and a concomitant, but proportionally smaller, reduction in AP-1 DNA binding was observed. Furthermore, treatment of squamous HBE cells with the retinoid SR11238, which inhibited AP-1 without activating retinoid receptor transcriptional properties, reduced the expression of transglutaminase type I and involucrin. These findings support the hypothesis that, in HBE cells, RAR and RXR signaling pathways inhibit AP-1 transcriptional activity, and this contributes to retinoid-induced reversal of HBE squamous differentiation.
0 Communities
1 Members
0 Resources
19 MeSH Terms