The Experts below are selected from a list of 15732 Experts worldwide ranked by ideXlab platform
Chawnshang Chang - One of the best experts on this subject based on the ideXlab platform.
-
Expression of the Orphan Receptor TR4 during brain development of the rat.
Brain research. Molecular brain research, 2000Co-Authors: Hermien S. A. Van Schaick, Chawnshang Chang, Judith G.m. Rosmalen, Sofia Lopes Da Silva, J. Peter H. BurbachAbstract:The Orphan Receptor TR4, member of the nuclear hormone Receptor family, is related to the Orphan Receptors TR2, COUP-TFI and ARP-1, and was originally cloned from the adult rat brain. The latter two Orphan Receptors have been implicated in central nervous system (CNS) development. To investigate a possible role for TR4 in brain development, expression of TR4 was studied in rat embryos. At embryonic days 14.5 and 19.5, high expression of TR4 was found in the CNS, while low expression was detected throughout the embryo. In postnatal rats, TR4 was mainly expressed in the hippocampus and cerebellum, resembling the expression pattern found in adult brain. These data show that like COUP-TFI and ARP-1, expression of TR4 becomes restricted to distinct areas. In adult brain, TR4 is predominantly expressed in granule cells of both hippocampus and cerebellum. The data suggest a possible role for TR4 during proliferation and maturation of brain structures.
-
Induction of TR4 Orphan Receptor by Retinoic Acid in Human HaCaT Keratinocytes
The Journal of investigative dermatology, 1999Co-Authors: Shigeki Inui, Yi-fen Lee, Anne R. Haake, Lowell A. Goldsmith, Chawnshang ChangAbstract:Human TR4 Orphan Receptor (TR4) can modulate the transcriptional activity of the reporter gene containing an AGGTCA direct repeat-hormone response element. Here we studied the potential role of TR4 in human HaCaT keratinocytes. Using a chloramphenicol acetyltransferase reporter gene assay, it was shown that TR4 can suppress retinoic acid-induced transactivation by 47.3% in human HaCaT keratinocytes. Electrophoretic mobility shift assay indicated that this suppression may be due to TR4 binding with higher affinity to the retinoic acid response element than retinoid Receptors. Western blot analysis further suggested that retinoic acid can increase the expression of TR4 protein in human HaCaT keratinocytes, indicating that TR4 acts as a negative feedback modulator for retinoic acid action. Interestingly, TR4 expression is increased in normal human keratinocytes when substituting a low calcium medium with a high calcium medium. Together, our data suggested, for the first time, that an Orphan Receptor, such as TR4, may play an important part in retinoid-mediated signaling pathways in human keratinocytes, providing a new insight into keratinocyte biology.
-
The genomic structure and chromosomal location of the human TR2 Orphan Receptor, a member of the steroid Receptor superfamily
Endocrine, 1998Co-Authors: Din-lii Lin, Chawnshang ChangAbstract:Human TR2 Orphan Receptor, isolated from the testis and prostate, is a member of the steroid/thyroid hormone Receptor superfamily. With the screening of a human genomic library and the combination of primer walking and PCR sequencing, we found that the entire TR2 Orphan Receptor gene coding region and 5′-untranslated region feature 13 introns and 14 exons, and that the consensus splice sequences (GT-AG) are present in all intron-exon boundaries. Within the region that codes for the DNA binding domain, TR2 Orphan Receptor gene has a distinct intron-exon junction. Whereas all other known steroid Receptors have one splice site that separates their first and second zinc fingers in the DNA binding domain, TR2 Orphan Receptor has a rare splice site located in the middle of its first zinc finger. The identification of specific junction sequences for potential alternative splicing sites helps to explain the existence of multiple forms of TR2 Orphan Receptor cDNA (TR2-5, 7, 9, 11). The S1 nuclease protection assay for TR2 message revealed that there are multiple transcription initiations, and that the major cap site surrounded by an initiator-like sequence is located at the 104th nucleotide upstream from the translation start codon. Sequence analysis of a 2.7-kb DNA fragment upstream of the TR2 Orphan Receptor translation start codon unveiled several potential cis -acting elements, such as AP-1, HNF-5, GATA1 binding sites, and GC boxes. Using fluorescence in situ hybridization combined with a high-resolution G-banding technique, we found that the TR2 Orphan Receptor gene was mapped to human chromosome 12 at band q22, whereas the structurally closely related TR4 Orphan Receptor gene was mapped to human chromosome 3 at band q24.3.
-
Induction of an intronic enhancer of the human ciliary neurotrophic factor Receptor (CNTFRα) gene by the TR3 Orphan Receptor
Endocrine, 1998Co-Authors: Win-jing Young, Yi-xun Liu, Hiroji Uemura, Chawnshang ChangAbstract:A hormone response element, CNTFRalpha-NBRE (5'-AAAGGTCA-3') has been identified in the fifth intron of the alpha component of ciliary neurotrophic factor Receptor gene (CNTFR-15) for the human TR3 Orphan Receptor (TR3). A specific binding between in vitro expressed TR3 and CNTFRalpha-NBRE was demonstrated by using electrophoretic mobility shift assay. A reporter gene assay using chloramphenicol acetyl-transferase (CAT) showed that CNTFR-15 has an enhancer activity that could be induced by TR3 in a dose-dependent manner. This induction was significantly reduced in the absence of CNTFRalpha-NBRE. Together, these results indicate CNTFRalpha-NBRE is sufficient to mediate TR3 action in inducing the enhancer activity of CNTFR-15. Our finding may, therefore, suggest CNTFRalpha is a target gene regulated by TR3 and expand the role of TR3 in the nervous system.
-
ANTISENSE TR3 Orphan Receptor CAN INCREASE PROSTATE CANCER CELL VIABILITY WITH ETOPOSIDE TREATMENT
Endocrinology, 1998Co-Authors: Hiroji Uemura, Chawnshang ChangAbstract:In androgen-responsive LNCaP human prostatic cancer cells, human TR3 Orphan Receptor, a member of the steroid Receptor superfamily, can be rapidly induced by androgen. In contrast, ablation of androgen by castration can induce the expression of the TR3 Orphan Receptor gene in rat ventral prostate that has undergone apoptosis. This phenomenon prompted us to further analyze the potential role of human TR3 Orphan Receptor in prostate cancer cells in which apoptosis had been induced. Northern blot analysis shows that human TR3 Orphan Receptor expression can be induced rapidly after treatment of LNCaP and PC-3 prostate cancer cells with calcium ionophore or etoposide. Our data further demonstrate that a much higher concentration of etoposide was needed to kill the same number of cells in LNCaP and PC-3 cells transfected stably with antisense TR3 Orphan Receptor compared with that in control vector transfectants. Together, our data suggest that the human TR3 Orphan Receptor may play an important role in modulating drug-induced prostate apoptosis.
H J Lee - One of the best experts on this subject based on the ideXlab platform.
-
Identification of the histamine H1 Receptor gene as a differentially repressed target of the human TR2 Orphan Receptor.
Molecular and cellular biochemistry, 1999Co-Authors: H J Lee, Y F Lee, C ChangAbstract:We have identified a DNA response element (TR2RE-HR) in the 3' flanking region of the human histamine H1 Receptor gene as a target for the TR2 Orphan Receptor, a member of the steroid/thyroid hormone Receptor superfamily. The application of both tetracycline inducible and improved differential display systems has allowed us to isolate a cDNA fragment differentially regulated by the expression of the TR2 Orphan Receptor. Northern blot and sequencing analysis demonstrated that the expression of the human histamine H1 Receptor gene was differentially repressed by the TR2 Orphan Receptor. Electrophoretic mobility shift assay further revealed a specific binding (dissociation constant = 26.2 nM) between the TR2 Orphan Receptor and the wildtype TR2RE-HR, but not the mutant TR2RE-HR. In addition, reporter gene expression assay indicated that the TR2 Orphan Receptor may suppress the expression of luciferase activities in a dose-dependent manner via the TR2RE-HR in HeLa cells. Our results demonstrate that the histamine H1 Receptor gene could represent one of the target genes directly regulated by the human TR2 Orphan Receptor.
-
Suppression of the human erythropoietin gene expression by the TR2 Orphan Receptor, a member of the steroid Receptor superfamily.
The Journal of biological chemistry, 1996Co-Authors: H J Lee, Win-jing Young, Charles C. Y. Shih, Chawnshang ChangAbstract:Abstract A DNA response element, TR2RE-EPO (5′-TCTGACCTCTCGACCTAC-3′) has been identified in the 3′-minimal hypoxia-inducible enhancer of the human erythropoietin gene for the TR2 Orphan Receptor, an androgen-repressed transcription factor and a member of the steroid/thyroid hormone Receptor superfamily. Electrophoretic mobility shift assay showed a specific binding with high affinity (K = 0.14 nM) between the TR2 Orphan Receptor and the TR2RE-EPO. Our data further indicated that this specific binding is not due to the homo-dimerization of the TR2 Orphan Receptor. In addition, reporter gene expression using chloramphenicol acetyltransferase assay demonstrated that the TR2 Orphan Receptor may suppress the expression of the chloramphenicol acetyltransferase activities via the TR2RE-EPO in the hypoxic/normoxic human hepatoma HepG2 cells. Finally, our in situ hybridization data also indicated that the TR2 Orphan Receptor and the erythropoietin transcripts can be co-expressed in mouse kidney and liver. Together, our data suggest that the human erythropoietin gene could represent the first human target gene regulated directly by the human TR2 Orphan Receptor.
-
Suppression of Gene Expression on the Simian Virus 40 Major Late Promoter by Human TR4 Orphan Receptor A MEMBER OF THE STEROID Receptor SUPERFAMILY
The Journal of biological chemistry, 1995Co-Authors: H J Lee, Yi-fen Lee, J. Peter H. Burbach, Chawnshang ChangAbstract:Abstract The key expression of the simian virus 40 (SV40) major late promoter could be repressed by the human TR4 Orphan Receptor via the +55 region of the SV40 major late promoter (nucleotide numbers 368-389, 5′-GTTAAGGTTCGTAGGTCATGGA-3′). Using the coupled in vitro transcribed and translated TR4 Orphan Receptor with a molecular mass of 67.3 kilodaltons, electrophoretic mobility shift assay showed specific binding with a dissociation constant of 1.09 nM between the TR4 Orphan Receptor and the SV40 +55 oligonucleotides. In addition, chloramphenicol acetyltransferase assay demonstrated that this SV40 +55 region can function as a repressor via the TR4 Orphan Receptor, suppressing the transcriptional activities of both SV40 early and late promoters. Together, our data suggest that the TR4 Orphan Receptor may play an important role for the suppression of the SV40 gene expression.
-
Identification of Human TR2 Orphan Receptor Response Element in the Transcriptional Initiation Site of the Simian Virus 40 Major Late Promoter
The Journal of biological chemistry, 1995Co-Authors: H J Lee, Chawnshang ChangAbstract:A DNA response element (TR2RE-SV40) for the TR2 Orphan Receptor, a member of the steroid-thyroid hormone Receptor superfamily, has been identified in the simian virus 40 (SV40) +55 region (nucleotide numbers 368-389, 5'-GTTAAGGTTCGTAGGTCATGGA-3'). Electrophoretic mobility shift assay, using in vitro translated TR2 Orphan Receptor with a molecular mass of 67 kilodaltons, showed a specific binding with high affinity (dissociation constant = 9 nM) for this DNA sequence. DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric Receptor AR/TR2/AR with the DNA-binding domain of the TR2 Orphan Receptor flanked by the N-terminal and androgen-binding domains of the androgen Receptor. In addition, this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters. Together, these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 Orphan Receptor that may function as a repressor for the SV40 gene expression.
-
the use of a dna binding domain replacement method for the detection of a potential tr3 Orphan Receptor response element in the mouse mammary tumor virus long terminal repeat
Biochemical and Biophysical Research Communications, 1993Co-Authors: H J Lee, John M Kokontis, Kaochung Wang, Chawnshang ChangAbstract:Abstract TR3 Orphan Receptor is a human homologue of the mouse nur77, N10 and rat NGF1-B, TIS1 genes which may represent an early response gene involved in the control of cell proliferation. We have studied potential target genes for TR3 Orphan Receptor using the DNA-binding domain replacement method. We found that mouse mammary tumor virus long terminal repeat-linked chloramphenicol acetyltransferase expression can be activated in transfected cells by a chimeric androgen Receptor/TR3 Orphan Receptor/androgen Receptor construct (AR/TR3/AR) in the presence of androgen. By deletion analysis, a region with 20 nucleotides in length between positions −1178 and −1159 of the mouse mammary tumor virus long terminal repeat was confirmed as a potential TR3 Orphan Receptor response element. These results suggest the feasibility of using the DNA-binding domain replacement method to detect target sequences of Orphan Receptors.
Yi-fen Lee - One of the best experts on this subject based on the ideXlab platform.
-
Induction of TR4 Orphan Receptor by Retinoic Acid in Human HaCaT Keratinocytes
The Journal of investigative dermatology, 1999Co-Authors: Shigeki Inui, Yi-fen Lee, Anne R. Haake, Lowell A. Goldsmith, Chawnshang ChangAbstract:Human TR4 Orphan Receptor (TR4) can modulate the transcriptional activity of the reporter gene containing an AGGTCA direct repeat-hormone response element. Here we studied the potential role of TR4 in human HaCaT keratinocytes. Using a chloramphenicol acetyltransferase reporter gene assay, it was shown that TR4 can suppress retinoic acid-induced transactivation by 47.3% in human HaCaT keratinocytes. Electrophoretic mobility shift assay indicated that this suppression may be due to TR4 binding with higher affinity to the retinoic acid response element than retinoid Receptors. Western blot analysis further suggested that retinoic acid can increase the expression of TR4 protein in human HaCaT keratinocytes, indicating that TR4 acts as a negative feedback modulator for retinoic acid action. Interestingly, TR4 expression is increased in normal human keratinocytes when substituting a low calcium medium with a high calcium medium. Together, our data suggested, for the first time, that an Orphan Receptor, such as TR4, may play an important part in retinoid-mediated signaling pathways in human keratinocytes, providing a new insight into keratinocyte biology.
-
Suppression of Gene Expression on the Simian Virus 40 Major Late Promoter by Human TR4 Orphan Receptor A MEMBER OF THE STEROID Receptor SUPERFAMILY
The Journal of biological chemistry, 1995Co-Authors: H J Lee, Yi-fen Lee, J. Peter H. Burbach, Chawnshang ChangAbstract:Abstract The key expression of the simian virus 40 (SV40) major late promoter could be repressed by the human TR4 Orphan Receptor via the +55 region of the SV40 major late promoter (nucleotide numbers 368-389, 5′-GTTAAGGTTCGTAGGTCATGGA-3′). Using the coupled in vitro transcribed and translated TR4 Orphan Receptor with a molecular mass of 67.3 kilodaltons, electrophoretic mobility shift assay showed specific binding with a dissociation constant of 1.09 nM between the TR4 Orphan Receptor and the SV40 +55 oligonucleotides. In addition, chloramphenicol acetyltransferase assay demonstrated that this SV40 +55 region can function as a repressor via the TR4 Orphan Receptor, suppressing the transcriptional activities of both SV40 early and late promoters. Together, our data suggest that the TR4 Orphan Receptor may play an important role for the suppression of the SV40 gene expression.
-
Gene expression of the androgen repressed rat TR2 Orphan Receptor: a member of steroid Receptor superfamily.
Endocrine, 1995Co-Authors: Ritsuro Ideta, Shuyuan Yeh, Yi-fen Lee, Kenji Adachi, Hiroyuki Takeda, Alan Saltzman, Chawnshang ChangAbstract:A full-length rat cDNA clone was obtained from the TR2 Orphan Receptor, a member of the steroid Receptor superfamily, using cDNA library screening and 3′ RACE-PCR technology. Under these conditions, only the TR2-11 form of the TR2 Orphan Receptor, the major form found in prostate, was identified. The overall amino acid homology between human and rat TR2-11 Orphan Receptors was near 90% with one amino acid difference in the DNA-binding domain sequence. Northern blot analysis identified multiple forms of the TR2 Orphan Receptor mRNAs expressed in human and rat prostates. Androgens repressed TR2 Orphan Receptor mRNA levels in human prostate LNCaP cells and rat ventral prostate. Polyclonal anti-TR2 Orphan Receptor antibodies raised from a unique TR2 Orphan Receptor 20 amino acid peptide were used to localize the TR2 Orphan Receptor in the nuclei of prostate and epididymis epithelium cells. Together, these data demonstrate that the TR2 Orphan Receptor can be expressed at mRNA and protein levels in the human and rat prostrates and may have some potential function in mediating androgen action in these tissues.
Francoise Bachelerie - One of the best experts on this subject based on the ideXlab platform.
-
the chemokine sdf 1 cxcl12 binds to and signals through the Orphan Receptor rdc1 in t lymphocytes
Journal of Biological Chemistry, 2005Co-Authors: Karl Balabanian, Bernard Lagane, Simona Infantino, Ken Y C Chow, Julie Harriague, Barbara Moepps, Fernando Arenzanaseisdedos, Marcus Thelen, Francoise BachelerieAbstract:Combined phylogenetic and chromosomal location studies suggest that the Orphan Receptor RDC1 is related to CXC chemokine Receptors. RDC1 provides a co-Receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the Receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a Receptor for CXCL12.
-
the chemokine sdf 1 cxcl12 binds to and signals through the Orphan Receptor rdc1 in t lymphocytes
Journal of Biological Chemistry, 2005Co-Authors: Karl Balabanian, Bernard Lagane, Simona Infantino, Ken Y C Chow, Julie Harriague, Barbara Moepps, Fernando Arenzanaseisdedos, Marcus Thelen, Francoise BachelerieAbstract:Abstract Combined phylogenetic and chromosomal location studies suggest that the Orphan Receptor RDC1 is related to CXC chemokine Receptors. RDC1 provides a co-Receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD ≈ 0.4 nm). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the Receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a Receptor for CXCL12.
Karl Balabanian - One of the best experts on this subject based on the ideXlab platform.
-
the chemokine sdf 1 cxcl12 binds to and signals through the Orphan Receptor rdc1 in t lymphocytes
Journal of Biological Chemistry, 2005Co-Authors: Karl Balabanian, Bernard Lagane, Simona Infantino, Ken Y C Chow, Julie Harriague, Barbara Moepps, Fernando Arenzanaseisdedos, Marcus Thelen, Francoise BachelerieAbstract:Combined phylogenetic and chromosomal location studies suggest that the Orphan Receptor RDC1 is related to CXC chemokine Receptors. RDC1 provides a co-Receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the Receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a Receptor for CXCL12.
-
the chemokine sdf 1 cxcl12 binds to and signals through the Orphan Receptor rdc1 in t lymphocytes
Journal of Biological Chemistry, 2005Co-Authors: Karl Balabanian, Bernard Lagane, Simona Infantino, Ken Y C Chow, Julie Harriague, Barbara Moepps, Fernando Arenzanaseisdedos, Marcus Thelen, Francoise BachelerieAbstract:Abstract Combined phylogenetic and chromosomal location studies suggest that the Orphan Receptor RDC1 is related to CXC chemokine Receptors. RDC1 provides a co-Receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD ≈ 0.4 nm). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the Receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a Receptor for CXCL12.