1
40
3
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.4155/fmc.12.72" target="_blank" rel="noreferrer noopener">http://doi.org/10.4155/fmc.12.72</a>
Pages
1307–1333
Issue
10
Volume
4
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Noncanonical mechanisms to regulate nuclear receptor signaling.
Publisher
An entity responsible for making the resource available
Future medicinal chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-06
Subject
The topic of the resource
Humans; Protein Binding; MicroRNAs/metabolism; Signal Transduction/drug effects; Ligands; DNA/metabolism; Peptides/chemistry/pharmacology; Small Molecule Libraries/chemistry/pharmacology; Receptors; Drug Evaluation; Preclinical; Cytoplasmic and Nuclear/antagonists & inhibitors/*metabolism
Creator
An entity primarily responsible for making the resource
Sadana Prabodh
Description
An account of the resource
Nuclear receptor (NR)-targeted therapies comprise a large class of clinically employed drugs. A number of drugs currently being used against this protein class were designed as structural analogs of the endogenous ligand of these receptors. In recent years, there has been significant interest in developing newer strategies to target NRs, especially those that rely on mechanistic pathways of NR function. Prominent among these are noncanonical means of targeting NRs, which include selective NR modulation, NR coactivator interaction inhibition, inhibition of NR DNA binding, modulation of NR cellular localization, modulation of NR ligand biosynthesis and downregulation of NR levels in target tissues. This article reviews each of these promising emerging strategies for NR drug development and highlights some of most significant successes achieved in using them.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.4155/fmc.12.72" target="_blank" rel="noreferrer noopener">10.4155/fmc.12.72</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Cytoplasmic and Nuclear/antagonists & inhibitors/*metabolism
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
DNA/metabolism
Drug Evaluation
Future medicinal chemistry
Humans
Ligands
MicroRNAs/metabolism
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
Peptides/chemistry/pharmacology
Preclinical
Protein Binding
Receptors
Sadana Prabodh
Signal Transduction/drug effects
Small Molecule Libraries/chemistry/pharmacology
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
1402–1412
Issue
9
Volume
42
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Nuclear receptor-mediated repression of human cholesterol 7alpha-hydroxylase gene transcription by bile acids.
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
2001
2001-09
Subject
The topic of the resource
Humans; Animals; Rats; Cell Line; Transfection; Liver/metabolism; Reverse Transcriptase Polymerase Chain Reaction; DNA/metabolism; CHO Cells; Cricetinae; Cholesterol 7-alpha-Hydroxylase/*genetics; Bile Acids and Salts/*pharmacology; *Membrane Glycoproteins; *Hydroxysteroid Dehydrogenases; Caco-2 Cells; Carrier Proteins/genetics/physiology; DNA-Binding Proteins/drug effects/genetics/physiology; Gene Expression/*drug effects; Kidney; Luciferases/genetics; Recombinant Fusion Proteins/metabolism; Retinoid X Receptors; Taurocholic Acid/pharmacology; Transcription Factors/drug effects/genetics/physiology; Cultured; Receptors; RNA; Genetic/drug effects; Messenger/analysis; Transcription; Genetic; Tumor Cells; Promoter Regions; Embryo; Cytoplasmic and Nuclear/genetics/*physiology; Mammalian; Retinoic Acid/genetics/physiology
Creator
An entity primarily responsible for making the resource
Chen W; Owsley E; Yang Y; Stroup D; Chiang J Y
Description
An account of the resource
Hydrophobic bile acids strongly repressed transcription of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) in the bile acid biosynthetic pathway in the liver. Farnesoid X receptor (FXR) repressed CYP7A1/Luc reporter activity in a transfection assay in human liver-derived HepG2 cells, but not in human embryonic kidney (HEK) 293 cells. FXR-binding activity was required for bile acid repression of CYP7A1 transcription despite the fact that FXR did not bind to the CYP7A1 promoter. FXR-induced liver-specific factors must be required for mediating bile acid repression. Bile acids and FXR repressed endogenous CYP7A1 but stimulated alpha-fetoprotein transcription factor (FTF) and small heterodimer partner (SHP) mRNA expression in HepG2 cells. Feeding of rats with chenodeoxycholic acid repressed CYP7A1, induced FTF, but had no effect on SHP mRNA expression in the liver. FTF strongly repressed CYP7A1 transcription in a dose-dependent manner, and SHP further inhibited CYP7A1 in HepG2 cells, but not in HEK 293 cells. FXR only moderately stimulated SHP transcription, whereas FTF strongly inhibited SHP transcription in HepG2 cells. Results revealed that FTF was a dominant negative factor that was induced by bile acid-activated FXR to inhibit both CYP7A1 and SHP transcription. Differential regulation of FTF and SHP expression by bile acids may explain the wide variation in CYP7A1 expression and the rate of bile acid synthesis and regulation in different species.
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Hydroxysteroid Dehydrogenases
*Membrane Glycoproteins
2001
Animals
Bile Acids and Salts/*pharmacology
Caco-2 Cells
Carrier Proteins/genetics/physiology
Cell Line
Chen W
Chiang J Y
CHO Cells
Cholesterol 7-alpha-Hydroxylase/*genetics
Cricetinae
Cultured
Cytoplasmic and Nuclear/genetics/*physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/drug effects/genetics/physiology
DNA/metabolism
Embryo
Gene Expression/*drug effects
Genetic
Genetic/drug effects
Humans
Journal of lipid research
Kidney
Liver/metabolism
Luciferases/genetics
Mammalian
Messenger/analysis
NEOMED College of Medicine
Owsley E
Promoter Regions
Rats
Receptors
Recombinant Fusion Proteins/metabolism
Retinoic Acid/genetics/physiology
Retinoid X Receptors
Reverse Transcriptase Polymerase Chain Reaction
RNA
Stroup D
Taurocholic Acid/pharmacology
Transcription
Transcription Factors/drug effects/genetics/physiology
Transfection
Tumor Cells
Yang Y
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
2192–2200
Issue
11
Volume
39
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors.
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
1998
1998-11
Subject
The topic of the resource
Animals; Rats; Transcription Factors/metabolism; Base Sequence; Molecular Sequence Data; DNA/metabolism; Cholesterol 7-alpha-Hydroxylase/*genetics; Hepatocyte Nuclear Factor 4; Mutagenesis; Luciferases/genetics; Retinoid X Receptors; Phosphoproteins/metabolism; COUP Transcription Factor II; COUP Transcription Factors; *Transcriptional Activation; Bile Acids and Salts/biosynthesis; DNA-Binding Proteins/metabolism; Hormones/*physiology; Oligonucleotide Probes/metabolism; Genes; Cultured; Receptors; Genetic; Cytoplasmic and Nuclear/*physiology; Tumor Cells; Reporter; Retinoic Acid/metabolism; Promoter Regions; Nucleic Acid; Site-Directed; *Receptors; Repetitive Sequences; Steroid
Creator
An entity primarily responsible for making the resource
Crestani M; Sadeghpour A; Stroup D; Galli G; Chiang J Y
Description
An account of the resource
The gene encoding cholesterol 7alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. Previously, we have identified two bile acid response elements (BARE) in the promoter of the CYP7A gene. The BARE II is located in nt -149/-118 region and contains three hormone response element (HRE)-like sequences that form two overlapping nuclear receptor binding sites. One is a direct repeat separated by one nucleotide DR1 (-146- TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123). Mutagenesis of these HRE sequences resulted in lower transcriptional activity of the CYP7A promoter/reporter genes in transient transfection assay in HepG2 cells. The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)1, binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold. Cotransfection of HNF-4 plasmid with another orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), synergistically activated the CYP7A transcription by 80-fold. The DR5 binds the RXR/RAR heterodimer. A hepatocyte nuclear factor-3 (HNF-3) binding site (-175-TGTTTGTTCT-166) was identified. HNF-3 was required for both basal transcriptional activity and stimulation of the rat CYP7A promoter activity by retinoic acid. Combinatorial interactions and binding of these transcription factors to BAREs may modulate the promoter activity and also mediate bile acid repression of CYP7A gene transcription.
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Receptors
*Transcriptional Activation
1998
Animals
Base Sequence
Bile Acids and Salts/biosynthesis
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/*genetics
COUP Transcription Factor II
COUP Transcription Factors
Crestani M
Cultured
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
DNA/metabolism
Galli G
Genes
Genetic
Hepatocyte Nuclear Factor 4
Hormones/*physiology
Journal of lipid research
Luciferases/genetics
Molecular Sequence Data
Mutagenesis
NEOMED College of Medicine
Nucleic Acid
Oligonucleotide Probes/metabolism
Phosphoproteins/metabolism
Promoter Regions
Rats
Receptors
Repetitive Sequences
Reporter
Retinoic Acid/metabolism
Retinoid X Receptors
Sadeghpour A
Site-Directed
Steroid
Stroup D
Transcription Factors/metabolism
Tumor Cells