A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.

A nuclear transcription factor. Heterodimerization with PPAR GAMMA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES.

Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.

Retinoid X Receptor beta (RXR-β) is a nuclear receptor protein that functions as a transcription factor, regulating gene expression in response to binding with retinoids and other signaling molecules, playing crucial roles in various biological processes including cell growth, differentiation, and metabolism.

A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization.

A nuclear transcription factor. Heterodimerization with PPAR ALPHA is important to metabolism of LIPIDS.

Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.

Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.

An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).

A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.

Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.

Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.

The process by which two molecules of the same chemical composition form a condensation product or polymer.

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin.

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.

Fluorinated hydrocarbons are organic compounds consisting primarily of carbon and fluorine atoms, where hydrogen atoms may also be present, known for their high stability, chemical resistance, and various industrial applications, including refrigerants, fire extinguishing agents, and electrical insulation materials.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.

A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and THYROID HORMONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in the transcriptional activation of chromatin regions.

Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.

Established cell cultures that have the potential to propagate indefinitely.

A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.

A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.

A COUP transcription factor that was originally identified as a homodimer that binds to a direct repeat regulatory element in the chicken albumin promoter. It is a transcription factor that plays an important role in EMBRYONIC DEVELOPMENT of the CENTRAL NERVOUS SYSTEM.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

A DNA sequence that is found in the promoter region of vitamin D regulated genes. Vitamin D receptor (RECEPTOR, CALCITRIOL) binds to and regulates the activity of genes containing this element.

TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.

Organic compounds which contain tin in the molecule. Used widely in industry and agriculture.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products.

Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.

A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.

A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1.

A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.

Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.

A subclass of retinol-binding proteins that take part in the intracellular storage and transport of RETINOL. They are both functionally and structurally distinct from PLASMA RETINOL-BINDING PROTEINS.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

A widely distributed purinergic P2X receptor subtype that plays a role in pain sensation. P2X4 receptors found on MICROGLIA cells may also play a role in the mediation of allodynia-related NEUROPATHIC PAIN.

Agents that soften, separate, and cause desquamation of the cornified epithelium or horny layer of skin. They are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases.

THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.

A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.

CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRB gene (also known as NR1A2, THRB1, or ERBA2 gene) as several isoforms produced by alternative splicing. Mutations in the THRB gene cause THYROID HORMONE RESISTANCE SYNDROME.

Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.

A highly malignant, primitive form of carcinoma, probably of germinal cell or teratomatous derivation, usually arising in a gonad and rarely in other sites. It is rare in the female ovary, but in the male it accounts for 20% of all testicular tumors. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, p1595)

A transcription factor that partners with ligand bound GLUCOCORTICOID RECEPTORS and ESTROGEN RECEPTORS to stimulate GENETIC TRANSCRIPTION. It plays an important role in FERTILITY as well as in METABOLISM of LIPIDS.

Benzopyrans saturated in the 2 and 3 positions.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

A sub-family of steroid receptor-related orphan nuclear receptors that have specificity for a variety of DNA sequences related to AGGTCA. COUP transcription factors can heterodimerize with a variety of factors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; and VITAMIN D RECEPTORS.

Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.

Transforming proteins encoded by erbA oncogenes from the avian erythroblastosis virus. They are truncated versions of c-erbA, the thyroid hormone receptor (RECEPTORS, THYROID HORMONE) that have retained both the DNA-binding and hormone-binding domains. Mutations in the hormone-binding domains abolish the transcriptional activation function. v-erbA acts as a dominant repressor of c-erbA, inducing transformation by disinhibiting proliferation.

A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.

A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension, and NEUROPATHIC PAIN. The receptor comprises three P2X3 subunits. The P2X3 subunits are also associated with P2X2 RECEPTOR subunits in a heterotrimeric receptor variant.

A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.

A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.

A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.

A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.

Organometallic compounds which contain tin and three alkyl groups.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.

An orphan nuclear receptor that is closely related to members of the thyroid-steroid receptor gene family. It was originally identified in NERVE CELLS and may play a role in mediation of NERVE GROWTH FACTOR-induced CELL DIFFERENTIATION. However, several other functions have been attributed to this protein including the positive and negative regulation of APOPTOSIS.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.

A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.

A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.

Proteins prepared by recombinant DNA technology.

A COUP transcription factor that negatively regulates GENETIC TRANSCRIPTION and competes with other hormone receptors for the common response element AGGTCA. It can also stimulate transcription of genes involved in the metabolism of GLUCOSE and CHOLESTEROL.

A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

A steroid hormone that regulates the processes of MOLTING or ecdysis in insects.

Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)

Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.

Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.

Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.

A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.

Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.

The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

Nucleic acid sequences involved in regulating the expression of genes.

A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.

Transport proteins that carry specific substances in the blood or across cell membranes.

A purinergic P2X neurotransmitter receptor found at high levels in the BRAIN and IMMUNE SYSTEM.

Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.

A cell line derived from cultured tumor cells.

Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.

An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.

A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.

Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.

Deletion of sequences of nucleic acids from the genetic material of an individual.

Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

Thiazoles are heterocyclic organic compounds containing a sulfur atom and a nitrogen atom, which are bound by two carbon atoms to form a five-membered ring, and are widely found in various natural and synthetic substances, including some pharmaceuticals and vitamins.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.

Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.

FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A continuous cell line that is a substrain of SWISS 3T3 CELLS developed though clonal isolation. The mouse fibroblast cells undergo an adipose-like conversion as they move to a confluent and contact-inhibited state.

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.

A 20-carbon branched chain fatty acid. In phytanic acid storage disease (REFSUM DISEASE) this lipid may comprise as much as 30% of the total fatty acids of the plasma. This is due to a phytanic acid alpha-hydroxylase deficiency.

A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

The active production and accumulation of VITELLINS (egg yolk proteins) in the non-mammalian OOCYTES from circulating precursors, VITELLOGENINS. Vitellogenesis usually begins after the first MEIOSIS and is regulated by estrogenic hormones.

An orphan nuclear receptor that is found at high levels in BRAIN tissue. The protein is believed to play a role in development and maintenance of NEURONS, particularly dopaminergic neurons.

Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.

Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.

The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.

A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS and PROGESTERONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in CHROMATIN REMODELING during the process of nuclear receptor-induced transcription. The coactivator has been found at elevated levels in certain HORMONE-DEPENDENT NEOPLASMS such as those found in BREAST CANCER.

The action of a drug in promoting or enhancing the effectiveness of another drug.

Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.

A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native trans-configuration.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRA gene (also known as NR1A1, THRA1, ERBA or ERBA1 gene) as several isoforms produced by alternative splicing.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.

A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.

A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.

Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.

A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.

A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.

Elements of limited time intervals, contributing to particular results or situations.