Sterol Regulatory Element Binding Proteins: Sterol regulatory element binding proteins are basic helix-loop-helix leucine zipper transcription factors that bind the sterol regulatory element TCACNCCAC. They are synthesized as precursors that are threaded into the MEMBRANES of the ENDOPLASMIC RETICULUM.CCAAT-Enhancer-Binding Proteins: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.Lipogenesis: De novo fat synthesis in the body. This includes the synthetic processes of FATTY ACIDS and subsequent TRIGLYCERIDES in the LIVER and the ADIPOSE TISSUE. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.DNA-Binding Proteins: 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.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Fatty Acid Synthases: Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.Orphan Nuclear Receptors: 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.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Gene Expression Regulation: 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.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Proprotein Convertases: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.Promoter Regions, Genetic: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Helix-Loop-Helix Motifs: Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Stearoyl-CoA Desaturase: An enzyme that catalyzes the formation of oleoyl-CoA, A, and water from stearoyl-CoA, AH2, and oxygen where AH2 is an unspecified hydrogen donor.Lipodystrophy, Familial Partial: Inherited conditions characterized by the partial loss of ADIPOSE TISSUE, either confined to the extremities with normal or increased fat deposits on the face, neck and trunk (type 1), or confined to the loss of SUBCUTANEOUS FAT from the limbs and trunk (type 2). Type 3 is associated with mutation in the gene encoding PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA.RNA, Messenger: 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.Leucine Zippers: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Nuclear Proteins: 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.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Hydrocarbons, FluorinatedReceptors, Cytoplasmic and Nuclear: 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.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)3T3-L1 Cells: 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.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Cell Line: Established cell cultures that have the potential to propagate indefinitely.PPAR alpha: 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.ATP Binding Cassette Transporter 1: 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.Farnesyl-Diphosphate Farnesyltransferase: The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.Transfection: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Protein Binding: 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.Cells, Cultured: 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.Acetyl-CoA Carboxylase: A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 184.108.40.206.TriglyceridesFatty Liver: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.Adipocytes: 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.Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.Triazenes: Compounds with three contiguous nitrogen atoms in linear format, H2N-N=NH, and hydrocarbyl derivatives.Desmosterol: An intermediate in the synthesis of cholesterol.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Genes, Reporter: 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.Cholestanols: Cholestanes substituted in any position with one or more hydroxy groups. They are found in feces and bile. In contrast to bile acids and salts, they are not reabsorbed.Phospholipid Ethers: Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues.Cell Nucleus: 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)Mice, Inbred C57BLSp1 Transcription Factor: Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.CCAAT-Binding Factor: A heterotrimeric DNA-binding protein that binds to CCAAT motifs in the promoters of eukaryotic genes. It is composed of three subunits: A, B and C.ATP-Binding Cassette Transporters: 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.Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Molecular Sequence Data: 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.Chromatin Immunoprecipitation: 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.Blotting, Western: 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.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Fatty Acid Synthase, Type I: Animal form of fatty acid synthase which is encoded by a single gene and consists of seven catalytic domains and is functional as a homodimer. It is overexpressed in some NEOPLASMS and is a target in humans of some ANTINEOPLASTIC AGENTS and some ANTI-OBESITY AGENTS.Mutation: 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.Signal Transduction: 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.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.Geranyltranstransferase: An enzyme involved in the MEVALONATE pathway, it catalyses the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate.Lamin Type A: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.HeLa Cells: 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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Schizosaccharomyces pombe Proteins: Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Sumoylation: A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.DNA Primers: 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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Adipogenesis: The differentiation of pre-adipocytes into mature ADIPOCYTES.Dibutyl Phthalate: A plasticizer used in most plastics and found in water, air, soil, plants and animals. It may have some adverse effects with long-term exposure.Simvastatin: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.Mice, Knockout: 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.Mice, Obese: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Inhibitors of Activated STAT: A family of structurally related proteins that are constitutively expressed and that negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. PIAS proteins inhibit the activity of signal transducers and activators of transcription.Down-Regulation: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.PPAR gamma: 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.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Protein Structure, Tertiary: 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.Luciferases: 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.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Blotting, Northern: 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.Electrophoretic Mobility Shift Assay: 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.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Adipocytes, Brown: Fat cells with dark coloration due to the densely packed MITOCHONDRIA. They contain numerous small lipid droplets or vacuoles. Their stored lipids can be converted directly to energy as heat by the mitochondria.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Response Elements: 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.Fatty Acids, Monounsaturated: Fatty acids which are unsaturated in only one position.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Amino Acid Sequence: 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.Fatty Acids, Unsaturated: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.Fasting: Abstaining from all food.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Lipodystrophy: A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.Oxidoreductases Acting on CH-CH Group Donors: A subclass of enzymes which includes all dehydrogenases acting on carbon-carbon bonds. This enzyme group includes all the enzymes that introduce double bonds into substrates by direct dehydrogenation of carbon-carbon single bonds.CCAAT-Enhancer-Binding Protein-alpha: A CCAAT-enhancer-binding protein found in LIVER; ADIPOSE TISSUE; INTESTINES; LUNG; ADRENAL GLANDS; PLACENTA; OVARY and peripheral blood mononuclear cells (LEUKOCYTES, MONONUCLEAR). Experiments with knock-out mice have demonstrated that CCAAT-enhancer binding protein-alpha is essential for the functioning and differentiation of HEPATOCYTES and ADIPOCYTES.Linoleic Acids, Conjugated: A collective term for a group of around nine geometric and positional isomers of LINOLEIC ACID in which the trans/cis double bonds are conjugated, where double bonds alternate with single bonds.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Progeria: An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.SUMO-1 Protein: A 1.5-kDa small ubiquitin-related modifier protein that can covalently bind via an isopeptide link to a number of cellular proteins. It may play a role in intracellular protein transport and a number of other cellular processes.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Feedback, Physiological: A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Endoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Up-Regulation: 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.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Cell Line, Tumor: A cell line derived from cultured tumor cells.DNA: 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).F-Box Proteins: A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Oscillometry: The measurement of frequency or oscillation changes.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Fats: The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (DIETARY FATS) as a source of energy. (Grant & Hackh's Chemical Dictionary, 5th ed)3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Feedback: A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.CCAAT-Enhancer-Binding Protein-delta: A member of the C-EBP protein family of transcription factors. It plays a key role in G0 PHASE mammary EPITHELIAL CELL growth arrest, and it is involved in transcriptional regulation of INTERLEUKIN 1; INTERLEUKIN 6; and TUMOR NECROSIS FACTOR-ALPHA.Lithium Chloride: A salt of lithium that has been used experimentally as an immunomodulator.CCAAT-Enhancer-Binding Protein-beta: A CCAAT-enhancer-binding protein found in LIVER; INTESTINES; LUNG and ADIPOSE TISSUE. It is an important mediator of INTERLEUKIN-6 signaling.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Ubiquitination: The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.Obesity, Morbid: The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.DNA, Complementary: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)Hypertriglyceridemia: A condition of elevated levels of TRIGLYCERIDES in the blood.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Plasmids: 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.DNA Footprinting: A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Acetylation: Formation of an acetyl derivative. (Stedman, 25th ed)Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Diet: Regular course of eating and drinking adopted by a person or animal.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Bile Acids and Salts: 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.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Sulfonamides: A group of compounds that contain the structure SO2NH2.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.COS Cells: 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).)MorpholinesDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Hyperlipidemias: Conditions with excess LIPIDS in the blood.ChromonesRecombinant Fusion Proteins: 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.MicroRNAs: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Cholesterol, LDL: Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Microarray Analysis: The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format.Histone Deacetylases: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.Thiazolidinediones: 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).Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 220.127.116.11.Lentivirus: A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Hypercholesterolemia: A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Cloning, Molecular: 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.
... and BHLHE40 are transcriptional targets of SREBP-1 (also known as ADD-1) isoforms SREBP-1a and SREBP-1c. After being ... BHLHE41 and BHLHE40 also repress SREBP-1. This forms a negative feedback loop between SREBP-1, BHLHE40, and BHLHE41 in muscles ... induced by SREBP-1, BHLHE41 and BHLHE40 have been shown to repress myogenesis by blocking MYOD1 transcription. BHLHE40 and ... that runs on a 24-hour circadian cycle, which has a 12-hour offset between SREBP-1 and BHLHE40/BHLHE41. In addition, BHLHE41 is ...
Fatty acid synthesis
SREBP (SREBP) 1.3.2 Family: Cell-cycle controlling factors; includes c-Myc 1.4 Class: NF-1 1.4.1 Family: NF-1 (A, B, C, X) 1.5 ... SREBP), which helps maintain proper lipid levels in the cell. Many transcription factors, especially some that are proto- ... SREBP, p53, orphan nuclear receptors II.B.3 cell membrane receptor-dependent - second messenger signaling cascades resulting in ...
Sterol regulatory element-binding protein 1
"Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport ... The isoforms are SREBP-1a and -1c (ADD-1). The proteins encoded by this gene are transcription factors that bind to a sequence ... SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell ... SREBP-1c regulates genes required for glucose metabolism and fatty acid and lipid production and its expression is regulated by ...
Citric acid cycle
Cyclin-dependent kinase 8
CDK8 phosphorylates the Notch intracellular domain, SREBP, and STAT1 S727. CDK8 also inhibits transcriptional activation by ... and SREBP. GRCh38: Ensembl release 89: ENSG00000132964 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000029635 - ... "Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1". The Journal of Clinical Investigation. 122 ...
Studies have found that an over expression of SREBP-1a or SREBP-1c in mouse liver cells results in the build-up of hepatic ... It is hypothesized that this effect occurs through the transcription factor SREBP-1, where the association of insulin and SREBP ... SREBP-2 has a well defined mode of action of the different members of this transcriptional family. At high levels of free ... Insulin induction of SREBP-1c is also involved in cholesterol metabolism. Experiments were conducted to study in vivo the over- ...
This control is exerted via the cyclic transcription of Insig2, encoding a trans-membrane protein that sequesters SREBP ... REV-ERBalpha participates in the circadian modulation of sterol regulatory element-binding protein (SREBP) activity, and ... September 2009). "REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis". PLoS Biol. 7 (9): e1000181 ... by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. Insig ...
Michael Stuart Brown
"Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport ... Oct 1993). "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein ... Wang X, Sato R, Brown MS, Hua X, Goldstein JL (Apr 1994). "SREBP-1, a membrane-bound transcription factor released by sterol- ... Sakai J, Duncan EA, Rawson RB, Hua X, Brown MS, Goldstein JL (Jun 1996). "Sterol-regulated release of SREBP-2 from cell ...
Basic helix-loop-helix leucine zipper transcription factors
Mir-133 microRNA precursor family
SREBP-1c mediates MEF2C downregulation through a mechanism that remains to be determined. As a consequence of lower MEF2C ... Altered activation of PI3K and SREBP-1c may explain the defective regulation of miR-1 and miR-133a expression in response to ... It is proposed that Insulin activates the translocation of SREBP-1c (BHLH) active form from the endoplasmic reticulum (ER) to ...
Sterol regulatory element-binding protein 2
SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade". Journal of Lipid Research. 41 (1): 99-108. PMID 10627507. Yang T, ... "Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport ... Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (Oct 1993). "SREBP-1, a basic-helix-loop-helix- ... Kan HY, Pissios P, Chambaz J, Zannis VI (Feb 1999). "DNA binding specificity and transactivation properties of SREBP-2 bound to ...
When cholesterol levels fall, SREBP is released from the nuclear membrane or endoplasmic reticulum, it then migrates to the ... Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins(SREBP). There is also ... SREBP). This is a transcription factor that is inactive when cholesterol levels are high, and active when cholesterol levels ...
When SREBP is inactive, it is bound to the ER or nuclear membrane with another protein called SREBP cleavage-activating protein ... If cholesterol levels rise, proteolytic cleavage of SREBP from the membrane ceases and any proteins in the nucleus are quickly ... Transcription of the reductase gene is enhanced by the sterol regulatory element binding protein (SREBP). This protein binds to ... SCAP). When cholesterol levels fall, SREBP is released from the membrane by proteolysis and migrates to the nucleus, where it ...
These studies suggest that mutations in SREBP-1c may increase the sensitivity to developing diabetes. Furthermore, SREBP-1c ... Later, SREBP-1c was identified as a candidate gene in the regulation of human insulin resistance. Two missense mutations in ... Studies in mice have shown that SREBP-1c mRNA expression was highly induced in mice having one polymorphism (-468 A/G) after ... Among them is the gene responsible for sterol response element binding protein-1c or SREBP-1c (a membrane-bound transcription ...
Membrane-bound transcription factor site-1 protease
SREBP cleavage-activating protein - Wikipedia
SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage". J. Biol. Chem. 284 (42): 28995-9004. doi:10.1074/jbc. ... Also, it binds SREBP by a series of consecutive WD repeats on its C-terminus. GRCh38: Ensembl release 89: ENSG00000114650 - ... 2008). "SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction". Atherosclerosis. 196 (2): 896-904. doi: ... Hua X, Nohturfft A, Goldstein JL, Brown MS (November 1996). "Sterol resistance in CHO cells traced to point mutation in SREBP ...
An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer | Nature Genetics
Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth and distant metastasis. Importantly, a high-fat ... The authors identify an aberrant SREBP prometastatic lipogenic program and show that a high-fat diet induces lipid accumulation ... We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a ... and an SREBP signature was highly enriched in metastatic human CaP. Thus, our findings uncover a prometastatic lipogenic ...
Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex. - PubMed - NCBI
Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage ... Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex.. Stewart EV1, Nwosu CC, Tong Z, Roguev A, Cummins TD ... The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme ... Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a ...
MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. - PubMed - NCBI
Human SREBP-1 (A) and SREBP-2 (B) genes harbor related intronic miRNAs (miR-33b and miR-33a, respectively). The sequences ... MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis.. Najafi-Shoushtari SH1, Kristo F, Li Y, ... C-E Expression profile of miR-33a/b and SREBP host genes in selected human tissues. Error bars represent experimental S.D. ... HDL miR-ed down by SREBP introns. [Science. 2010]. *Cardiovascular disorders: MicroRNA modulation of cholesterol. [Nat Rev Drug ...
SREBP-1 Antibody (39939)
Active Motif Anti-SREBP-1 Monoclonal (IgG-2A4), Catalog # 39939. Tested in Western Blot (WB), Immunoprecipitation (IP), ChIP ... SREBP-1a and SREBP-1c (originally cloned as ADD1) are protein products of alternative promoter usage of the SREBP-1 gene. The ... Cite SREBP-1 Monoclonal Antibody (IgG-2A4). The following product was used in this experiment: SREBP-1 Monoclonal Antibody (IgG ... This SREBP-1 antibody was raised against a recombinant protein corresponding to amino acids 301-407 of human SREBP-1. ...
SREBP Controls Oxygen-Dependent Mobilization of Retrotransposons in Fission Yeast
An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer
... Nat Genet. 2018 Feb;50(2):206-218. doi: ... Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth and distant metastasis. Importantly, a high-fat ... We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a ... and an SREBP signature was highly enriched in metastatic human CaP. Thus, our findings uncover a prometastatic lipogenic ...
IJMS | Free Full-Text | SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction
Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of ... We conclude that CR induces SREBP-1c-dependent metabolic remodeling, including the enhancement of FA biosynthesis and ... SREBP-1c), a master regulator of FA synthesis, as a mediator of CR. These findings were validated by showing that CR failed to ... upregulate factors involved in FA biosynthesis and to extend longevity in SREBP-1c knockout mice. ...
Small-molecule inhibitors of SREBP activation - potential for new treatment of metabolic disorders - MedChemComm (RSC...
Aberrant SREBP activity has been linked to metabolic disease states, such as obesity, fatty liver, insulin resistance, ... Thus, inhibition of SREBP activation is a potential therapeutic approach to treating metabolic disorders. This review focuses ... Small-molecule inhibitors of SREBP activation - potential for new treatment of metabolic disorders M. Watanabe and M. Uesugi, ... Small-molecule inhibitors of SREBP activation - potential for new treatment of metabolic disorders ...
SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c | Diabetes
3E). Besides, mRNA levels of SREBP-1a, SREBP-2, Scap, and Insig1 were not altered (Fig. 3F). Furthermore, the increased ... H: Representative protein levels of full-length (FL-) SREBP-1, nuclear (N-) SREBP-1, FASN, and ACC1 in the livers of ob/ob mice ... The transcriptional activity and functional SOX4 binding motif of the SREBP-1c promoter. A: Relative mRNA levels of SREBP-1c in ... our data suggest that Sox4 is not only required for the basal expression of SREBP-1c but also required for induced SREBP-1c ...
SREBP: A Key Effector of mTORC1 Signaling in Metabolism and Cancer
SREBP). We have demonstrated that mTORC1 stimulates the accumulation of processed, active SREBP, although details of the ... SREBP: A Key Effector of mTORC1 Signaling in Metabolism and Cancer. Doctoral dissertation, Harvard University. ... demonstrate that mTORC1 plays a role downstream of TSC-deficiency and oncogenic PIK3CA and K-Ras to activate lipogenic SREBP ...
Palmitate Impairs and Eicosapentaenoate Restores Insulin Secretion Through Regulation of SREBP-1c in Pancreatic Islets |...
SREBP-1c mRNA was highly induced by palmitate and completely suppressed by EPA but not SREBP-1a mRNA (Fig. 2A). These changes ... SREBP-1c plays a dominant role in palmitate-EPA effects on insulin secretion.. The contribution of SREBP-1c to palmitate-EPA ... 6D). Taken together with partial regulation of UCP-2 in SREBP-1-null islets (Fig. 4A), effects of UCP-2 and SREBP-1c on GSIS ... CONCLUSIONS-SREBP-1c plays a dominant role in palmitate-mediated insulin secretion defect, and EPA prevents it through SREBP-1c ...
SREBP‑2 expression pattern contributes to susceptibility of Mongolian gerbils to hypercholesterolemia
Li, C., Guo, H., Dai, F., Huo, X., Li, Z., Zhang, S., Fu, R., He, Z., Gu, M., Du, X., Chen, Z.SREBP‑2 expression pattern ... Li, C., Guo, H., Dai, F., Huo, X., Li, Z., Zhang, S., Fu, R., He, Z., Gu, M., Du, X., Chen, Z.SREBP‑2 expression pattern ... SREBP‑2 expression pattern contributes to susceptibility of Mongolian gerbils to hypercholesterolemia. *Authors: *Changlong Li ... Serum lipid levels and hepatic fat deposition were measured, and mRNA and protein levels of SREBP‑2 and HMGCR were evaluated by ...
Activation of gene expression by SREBF (SREBP) (Homo sapiens) - WikiPathways
Rome S, Lecomte V, Meugnier E, Rieusset J, Debard C, Euthine V, Vidal H, Lefai E.; Microarray analyses of SREBP-1a and SREBP- ... Activation of gene expression by SREBF (SREBP) (Homo sapiens). From WikiPathways. Revision as of 10:46, 18 November 2015 by ... Nagai M, Sakakibara J, Nakamura Y, Gejyo F, Ono T.; SREBP-2 and NF-Y are involved in the transcriptional regulation of ... Shin ES, Lee HH, Cho SY, Park HW, Lee SJ, Lee TR.; Genistein downregulates SREBP-1 regulated gene expression by inhibiting ...
Sterol Regulatory Element-Binding Proteins (SREBP) signalling (Homo sapiens) - WikiPathways
SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage.; J Biol Chem, 2009 PubMed Europe PMC Scholia*Peterson ... SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its dissociation from SREBP cleavage-activating protein (SCAP ... Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS; SREBP-1, a basic-helix-loop-helix-leucine zipper ... Chen G, Liang G, Ou J, Goldstein JL, Brown MS; Central role for liver X receptor in insulin-mediated activation of Srebp-1c ...
IJMS | Free Full-Text | SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular...
In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor- ... SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p , 0.05). In ... SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions ... These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell ...
Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE−/− Mice Fed with a High-Fat Diet
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake |...
... leading to activation of SREBP-1 and SREBP-2, and knockdown experiments indicate the importance of both SREBP-1 and SREBP-2 on ... B) Immunoblot of SREBP-2 cleavage in T47D cells treated as in (A). p, uncleaved SREBP-2 precursor; m, cleaved SREBP-2 mature ... and SREBP-1-dependent tumor survival pathway by increasing LDLR in GBM through SREBP-1 but not SREBP-2 (27). Targeting LDLR ... so NRG1 can still induce SREBP-2 cleavage despite reduced expression of SREBP-2. NRG1 did not affect SREBP-2 cleavage at the 6- ...
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake |...
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake ... Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake ... Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake ... Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake ...
Frontiers | Astragaloside IV Inhibits Triglyceride Accumulation in Insulin-Resistant HepG2 Cells via AMPK-Induced SREBP-1c...
AMPK-induced SREBP-1c phosphorylation is crucial for proper regulation of lipid metabolism in the liver. Astragaloside IV (AST ... We also investigated whether phosphorylation of SREBP-1c at Ser372 was required for AST function.Results: We found that AST ... We also investigated whether phosphorylation of SREBP-1c at Ser372 was required for AST function. Results: We found that AST ... AST also inhibited translocation of SREBP-1c into the nucleus of insulin resistant HepG2 cells by inducing phosphorylation of ...
Molecular Mechanisms of Mitigation of Insulin Induction of SREBP-1c by N-3 PUFA
Species about Molecular Mechanisms of Mitigation of Insulin Induction of SREBP-1c by N-3 PUFA ... SREBP-1 products*CISH products*DAND5 products*Sp1 products*PSG1 products*CD36 products*FAT1 products*OPN1LW products*eIF4E ... Molecular Mechanisms of Mitigation of Insulin Induction of SREBP-1c by N-3 PUFA. Summary. Principal Investigator: Marshall B ... Specifically, we have been studying the insulin-responsive cis-acting elements of the rat SREBP-1c promoter and have found that ...
pGreenFire1-SREBP Lentivector | System Biosciences
Study SREBP signal transduction by co-expressing dscGFP and luciferase in response to SREBP activity. ... The pGreenFire1-SREBP Lentivector co-expresses a destabilized copepod GFP (dscGFP; 2-hour half-life) and luciferase from SREBP ... 2019) SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun. 2019 Jan 10; 10(1):120. PM ID: ... The result is the ability to quantitatively measure SREBP activity by fluorescence and luciferase activity.. ...
Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway
Insulin induced gene-1 (Insig-1) is a critical upstream regulatory factor of SREBP-1c. Insig-1 prevents the SREBP cleavage- ... subsequently decreases nuclear SREBP-1c (nSREBP-1c) expression, and blocks the related gene transcription of SREBP-1c. It has ... both in vivo and in vitro studies have demonstrated that the overexpression of SREBP-1c impairs insulin secretion (30). SREBP- ... SREBP-1c stimulates UCP-2 expression in β cells under a high nutrition state (33). In our study, Insig-1 expression was ...
Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth...
... accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP ... Lipid-loaded VSMC exposed to N-acetyl- Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear ... Translocation and the expression of sterol response element-binding protein-1 (SREBP-1) were indirectly detected by an ... Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth ...
Collaborative effects of chlorogenic acid and caffeine on lipid metabolism via the AMPKα-LXRα/SREBP-1c pathway in high-fat diet...
Collaborative effects of chlorogenic acid and caffeine on lipid metabolism via the AMPKα-LXRα/SREBP-1c pathway in high-fat diet ... Collaborative effects of chlorogenic acid and caffeine on lipid metabolism via the AMPKα-LXRα/SREBP-1c pathway in high-fat diet ... SREBP-1c and LXRα), and decreased the expressions of FAS and HMGR. Besides, the expressions of ACO, ATGL and HSL were increased ... caffeine had anti-obesity effects and regulated lipid metabolism in high-fat diet-induced obese mice via the AMPKα-LXRα/SREBP- ...
Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARalpha and SREBP-1c signaling.
SREBP-1c is a member of the family of SREBP membrane-bound transcription factors. It activates mainly the transcription of ... mainly through downregulation of SREBP-1c and its target gene . Interestingly, we found that the SREBP-1c mRNA expression ... The expression of hepatic SREBP-1C, FAS, ME and G6PDH in rats fed Con or OA diet or the diet with OA+0.05% SSC for 10 d. Data ... Overexpression of SREBP-1c produces a pronounced elevation of hepatic TG concentrations leading to the development of NAFLD [27 ...
Effect of an enriched cholesterol diet during gestation on fatty acid synthase, HMG-CoA reductase and SREBP-1/2 expressions in...
Effect of an enriched cholesterol diet during gestation on fatty acid synthase, HMG-CoA reductase and SREBP-1/2 expressions in ... In the placenta, SREBPs are highly expressed, and the ECD supplementation increased nuclear SREBP-1/2 protein levels. In ... HMGR and SREBP-1/2, which are involved in either lipid or cholesterol synthesis. We confirmed that gestation modifies the ... it would be interesting to find which genes are then targeted by SREBP-1/2 during gestation.. ...
Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2...
Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1
The three isoforms of SREBP precursors located on the endoplasmic reticulum membrane, designated SREBP-1a, SREBP-1c, and SREBP- ... SSW causes SREBP-1 activation. (A) Time-dependence of SREBP expression and activation. AML 12 cells were treated with 1:40 SSW ... To confirm that SSW affects SREBP-1 function but not that of SREBP-2, we performed RT-PCR on cells exposed to SSW and examined ... 3A). Furthermore, there was also a dose-dependent expression and activation of SREBP-1, but not SREBP-2 (Fig. 3B). The ...
Xanthohumol Improves Diet-induced Obesity and Fatty Liver by Suppressing Sterol Regulatory Element-binding Protein (SREBP)...
Expression plasmids for SREBP-1a and SREBP-2 (pCMV-3×FLAG-SREBP-1a(2-487) and pCMV-3×FLAG-SREBP-2 (2-481)) were previously ... There are three major SREBP isoforms in mammals, SREBP-1a, -1c, and -2 (8). SREBP-1a and -1c mainly activate the expression of ... XN inhibits SREBP processing in the liver of HFD-fed mice. A, immunoblot (IB) analysis of liver extracts with anti-SREBP-1 (H- ... XN Suppresses SREBP Processing by Blocking ER-to-Golgi Transport of the SCAP/SREBP Complex Next, we investigated the mechanism ...
LipogenesisProteinRegulationHepaticBiosynthesisRegulatesGene expressionExpressionTarget genesLipogenicOverexpressionFattyActivationHomeostasisSREBPsIsoformsHMGCRUpregulationDownstreamNuclear SREBP-1cScap dissociates from InsigTranslocationPromoterAccumulationBindsSite 1 proteaKnockdownInhibition of SREBPEndoplasmicInsulinMicePhosphorylationGolgiAMPKSterolsTranscriptional activityMetabolismMembrane-bound transcription factorDegradationMonoclonal AntibodyActivateInsigProteinsPolyclonalNucleus
- 2009). "Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? (wikipedia.org)
- Fig. 6: SREBP-dependent lipogenesis is critical for PML -loss-induced CaP growth and metastasis. (nature.com)
- At the molecular level, de novo lipogenesis is mainly regulated by transcription factors, SREBP-1c and carbohydrate response element-binding protein (ChREBP), which are activated by insulin and glucose, respectively ( 6 , 7 ). (diabetesjournals.org)
- Induction of the pentose phosphate pathway and de novo lipogenesis is achieved by activation of a transcriptional program affecting metabolic gene targets of sterol regulatory element-binding protein (SREBP). (harvard.edu)
- In cancer, our initial findings demonstrate that mTORC1 plays a role downstream of TSC-deficiency and oncogenic PIK3CA and K-Ras to activate lipogenic SREBP targets and de novo lipogenesis. (harvard.edu)
- We investigated its mechanisms, focusing on contribution of SREBP-1c, a key transcription factor for lipogenesis. (diabetesjournals.org)
- In addition, the inhibited SREBP-1c- mediated lipogenesis caused by SSC may also contribute to alleviating fatty liver. (biomedsearch.com)
- These data suggest that Rev-erb beta has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis. (garvan.org.au)
- Although PI3K-AKT-mTORC1-p70S6K-signaling kinases are known to drive feed-forward expression of SREBP-1c, the identity of the phosphorylated amino acid residue(s) putatively involved in insulin-stimulated de novo lipogenesis remains elusive. (elsevier.com)
- Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. (biomedcentral.com)
- Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. (biomedcentral.com)
- SREBP-1c is responsible for regulating the genes required for de novo lipogenesis. (wikipedia.org)
- Sterol regulatory element-binding protein cleavage-activating protein, also known as SREBP cleavage-activating protein or SCAP is a protein that in humans is encoded by the SCAP gene. (wikipedia.org)
- SCAP is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP). (wikipedia.org)
- Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. (nih.gov)
- Lovastatin/β-cyclodextrin-mediated depletion of cholesterol in J774 mouse macrophages results in increased expression of ( A ) SREBP-2 and ( B ) miR-33a, and ( C ) in decreased ABCA1 protein levels. (nih.gov)
- This SREBP-1 antibody was raised against a recombinant protein corresponding to amino acids 301-407 of human SREBP-1. (thermofisher.com)
- SREBP-1a and SREBP-1c (originally cloned as ADD1) are protein products of alternative promoter usage of the SREBP-1 gene. (thermofisher.com)
- Upon activation, the SREBP protein is translocated to the Golgi and proteolytic cleavage occurs resulting in a mature transcriptionally active 60-78 kDa fragment. (thermofisher.com)
- Previously, using microarray analysis of WAT from CR rats, we found that CR enhances fatty acid (FA) biosynthesis, and identified sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA synthesis, as a mediator of CR. (mdpi.com)
- Concomitantly, palmitate activated and EPA abolished both mRNA and nuclear protein of SREBP-1c, accompanied by reciprocal changes of SREBP-1c target genes such as insulin receptor substrate-2 (IRS-2) and granuphilin. (diabetesjournals.org)
- Uncoupling protein-2 (UCP-2) also plays a crucial role in the palmitate inhibition of insulin secretion, as confirmed by knockdown experiments, but SREBP-1c contribution to UCP-2 regulation was partial. (diabetesjournals.org)
- Sterol regulatory element-binding protein (SREBP)-1c is a membrane-bound transcription factor of the basic helix loop helix leucine zipper family and has been established as a regulator of lipogenic enzymes in the liver ( 16 , 17 ). (diabetesjournals.org)
- The present study aimed to explore the role of sterol regulatory element binding protein (SREBP)‑2 and 3‑hydroxy‑3‑methylglutaryl CoA reductase (HMGCR) in hypercholesterolemia susceptibility in gerbils. (spandidos-publications.com)
- Serum lipid levels and hepatic fat deposition were measured, and mRNA and protein levels of SREBP‑2 and HMGCR were evaluated by quantitative polymerase chain reaction and Western blotting. (spandidos-publications.com)
- Sterol regulatory element-binding protein (SREBP) are membrane-bound proteins that act as transcription factors. (wikipathways.org)
- Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs. (wikipathways.org)
- Insulin enhances the biogenesis of nuclear sterol regulatory element-binding protein (SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its dissociation from SREBP cleavage-activating protein (SCAP).SREBP-1c complex. (wikipathways.org)
- Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. (mdpi.com)
- We found that ERBB4 activates sterol regulatory element binding protein-2 (SREBP-2) to enhance low-density lipoprotein (LDL) uptake and cholesterol biosynthesis. (sciencemag.org)
- AMP-activated protein kinase (AMPK)-induced sterol regulatory element binding protein-1c (SREBP-1c) phosphorylation is crucial for proper regulation of lipid metabolism in the liver. (frontiersin.org)
- We evaluated glucose, triglyceride (TG), and non-esterified fatty acid (NEFA) production, as well as SREBP-1c transcription, SREBP-1c protein expression, and downstream gene expression with or without the presence of AST. (frontiersin.org)
- Our hypothesis is that insulin increases production of fat (triglyceride) in such individuals by increasing levels of a protein called sterol regulatorybinding-protein-1c or SREBP-1c. (labome.org)
- Sterol regulatory element binding protein-1c (SREBP-1c), a key nuclear transcription factor that regulates lipid metabolism, has been proven to play a role in insulin secretion. (spandidos-publications.com)
- In recent years, sterol regulatory element binding protein-1c (SREBP-1c), an important lipogenic transcription factor ( 6 ), has been found to regulate genes involving insulin secretion ( 7 ). (spandidos-publications.com)
- Insig-1 prevents the SREBP cleavage-activating protein (SCAP)/SREBP-1c complex to translocate from the Golgi apparatus to the endoplasmic reticulum (ER), subsequently decreases nuclear SREBP-1c (nSREBP-1c) expression, and blocks the related gene transcription of SREBP-1c. (spandidos-publications.com)
- Translocation and the expression of sterol response element-binding protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. (nih.gov)
- SSC also decreased the gene expression of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c). (biomedsearch.com)
- In the placenta, SREBPs are highly expressed, and the ECD supplementation increased nuclear SREBP-1/2 protein levels. (biomedsearch.com)
- SSW increases lipid accumulation in hepatocytes by modulating the activity of 5′-AMP-activated protein kinase (AMPK) and sterol response element binding protein-1 (SREBP-1), two critical molecules involved in lipid synthesis. (pubmedcentralcanada.ca)
- Our results suggest that XN impairs the endoplasmic reticulum-to-Golgi translocation of the SREBP cleavage-activating protein (SCAP)-SREBP complex by binding to Sec23/24 and blocking SCAP/SREBP incorporation into common coated protein II vesicles. (pubmedcentralcanada.ca)
- In cells with low sterol levels, SREBP cleavage-activating protein (SCAP) binds to Sec23/24, which clusters the SCAP/SREBP complex into common coated protein II (COP II) vesicles ( 4 ). (pubmedcentralcanada.ca)
- SCAP (SREBP cleavage-activating protein) forms a complex with sterol regulatory element-binding proteins (SREBPs) and escorts them from the endoplasmic reticulum (ER) to the Golgi complex where proteases release transcriptionally active segments of SREBPs, which enter the nucleus to activate lipid synthesis. (eurekamag.com)
- We interpret these findings to indicate that sterols cause the SCAP.SREBP complex to bind to an ER retention protein through an interaction that involves the sterol-sensing domain. (eurekamag.com)
- The SCAP(TM1-6) segment competes with the SCAP.SREBP complex for binding to this putative retention protein, thereby liberating the SCAP.SREBP complex so that it can move to the Golgi despite the presence of sterols. (eurekamag.com)
- The present study was to investigate whether the mRNA levels of the transcription factors, sterol regulatory element-binding protein-2 (SREBP-2), peroxisome proliferator-activated receptor-δ (PPARδ) as well as slow type myosin heavy chain (MYH7) gene are modulated after exhaustive exercise and if so, whether such alterations are related to the percentage of MHC isoforms. (jyu.fi)
- When cellular sterol levels are high, Scap binds an ER retention protein, Insig, which retains the SREBP/Scap complex in the ER. (elifesciences.org)
- Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 18.104.22.168) pipeline Target constitutes close to 16 molecules. (researchmoz.us)
- It also reviews key players involved in Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 22.214.171.124) targeted therapeutics development with respective active and dormant or discontinued projects. (researchmoz.us)
- In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. (inserm.fr)
- SREBP-1 (Ab-439) antibody detects endogenous levels of total SREBP-1 protein. (mybiosource.com)
- Insulin stimulates de novo lipid synthesis in the liver and in cultured hepatocytes via its ability to activate sterol regulatory element-binding protein 1c (SREBP-1c). (elsevier.com)
- Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. (biomedcentral.com)
- To gain further insights into the molecule mechanism by which SSC alters gene expression of hepatic lipids metabolism, sterol-regulatory element binding protein (SREBP-1c) mRNA, the principal regulator of hepatic fatty acid biosynthesis, was determined. (biomedcentral.com)
- PF 429242 is a reversible, competitive inhibitor of sterol regulatory element-binding protein (SREBP) site 1 protease. (adooq.cn)
- Fatostatin is an inhibitor of sterol regulatory element binding protein (SREBP). (adooq.cn)
- sterol regulatory element binding protein, SREBP), które stymuluje syntezę kwasów tłuszczowych w wątrobie, oraz kinazy białkowej aktywowanej przez AMP (ang. (kopalniawiedzy.pl)
- The SREBP cleavage activating protein (SCAP) and the INSIG proteins are essential in this regulatory process. (ucc.ie)
- Here we have investigated the effect of hypoxia and serum deprivation on sterol regulatory element-binding protein (SREBP) activity and the expression of lipid metabolism genes in human glioblastoma multiforme (GBM) cancer cells. (ox.ac.uk)
- Moreover, expression of stearoyl-CoA desaturase, the enzyme required for the generation of mono-unsaturated fatty acids, and fatty acid-binding protein 7, a regulator of glioma stem cell function, was strongly dependent on SREBP function. (ox.ac.uk)
- These aP2-SREBP-1c mice express a transgene that overexpresses human nuclear sterol regulatory element binding protein-1c in adipose tissue under the control of the adipocyte-specific aP2 promoter, resembling congenital generalized lipodystrophy in humans. (jax.org)
- SREBP precursors are retained in the ER membranes through a tight association with SCAP and a protein of the INSIG family. (wikipedia.org)
- The ~120 kDa SREBP precursor protein is anchored in the membranes of the endoplasmic reticulum (ER) and nuclear envelope by virtue of two membrane-spanning helices in the middle of the protein . (wikipedia.org)
- However, the anchor protein of Scap/SREBP in the Golgi is unknown. (antibodychain.com)
- Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 ( PAQR3 ) interacts with Scap and SREBP and tethers them to the Golgi. (antibodychain.com)
- Hexacosanol also suppressed the nuclear translocation and activation of sterol regulatory element-binding protein-2 (SREBP-2), a key transcription factor in cholesterol biosynthesis. (naturalnews.com)
- Based on these results, the researchers concluded that the hypocholesterolemic activity of hexacosanol is due to its ability to regulate AMPK activation and suppress SREBP-2, which causes the inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase mRNA expression and protein activity. (naturalnews.com)
- Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) family of transcription factors, is synthesized as a 125 kd precursor that is attached to the nuclear envelope and endoplasmic reticulum. (elsevier.com)
- The liver biopsies were analyzed for total lipid content and protein expression of insulin receptor beta (IR beta), fatty acid translocase (FAT/CD36) and sterol regulatory element-binding protein-1 (SREBP-1). (ac.rs)
- 4) hepatic expressions of low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1 (HNF1) were examined by real time quantitative polymerase chain reaction (RT-PCR) and western blotting analysis. (biomedcentral.com)
- Moreover, it was postulated that statins increased the activity/nuclear translocation of SREBP-2, resulting in the increased expression and secretion of the PCSK9 protein. (biomedcentral.com)
- Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP) Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP) Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone. (wizdom.ai)
- Finally, both insulin treatment and overexpression of SRE binding protein (SREBP-1) increase the CIC transcript and protein levels, whereas PUFA have an opposite effect. (uniba.it)
- The membrane-bound transcription factor sterol regulatory element binding protein (SREBP) upregulates enzymes required for cholesterol biosynthesis in response to cellular cholesterol depletion. (hopkinsmedicine.org)
- Sterol regulatory element-binding protein (SREBP) cleavage regulates Golgi-to-endoplasmic reticulum recycling of SREBP cleavage-activating protein (SCAP). (hopkinsmedicine.org)
- Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to control sterol homeostasis. (hopkinsmedicine.org)
- Binding of SREBP to SRE induces transcription of specific genes, leading to an increase in the mRNA and corresponding protein. (nap.edu)
- The processing of SREBP-2 protein was promoted by phorbol 12-myristate 13-acetate (PMA) in the hepatic cells WRL and HepG2, and the increased processing was reversed by apigenin or luteolin co-administration. (edu.hk)
- Reciprocal regulation by cholesterol and SREBP/miR-33. (nih.gov)
- SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase. (wikipathways.org)
- DESCRIPTION (provided by applicant): Understanding the mechanistic basis of chronic aberrant regulation of SREBP-1c and its downstream lipogenic enzyme targets in chronic hyperinsulinemic states has been a focus of research in our laboratory. (labome.org)
- SREBP-1c preferentially controls the expression of genes involved in triglyceride synthesis and accumulation, such as fatty acid synthase (FAS) and acetyl coenzyme-A carboxylase (ACC), whereas SREBP-2 activity has been more closely linked to regulation of genes involved in cholesterol synthesis and uptake, such as low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) [ 14 - 18 ]. (pubmedcentralcanada.ca)
- Up-regulation of the expression and processing of SREBP-1c has been observed in the liver of obese mice ( 9 , 10 ), and liver-specific SREBP-1c transgenic mice have displayed hepatic steatosis, hypertriglyceridemia, and insulin resistance ( 11 ). (pubmedcentralcanada.ca)
- Here, we report that A. fumigatus SREBP, SrbA, mediates regulation of iron acquisition in response to hypoxia and low iron conditions. (prolekare.cz)
- These results support a role for SREBP-mediated iron regulation in fungal virulence, and they lay a foundation for further exploration of SREBP's role in iron homeostasis in other eukaryotes. (prolekare.cz)
- Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. (inserm.fr)
- The aim of this thesis is to further characterise the molecular and cellular aspects surrounding regulation of SREBP processing. (ucc.ie)
- No difference in either the regulation of SREBP processing or HMGCR degradation between the INSIG1 isoforms was observed and the functional significance of the two isoforms is as yet unclear. (ucc.ie)
- Down regulation of SREBP processing by sterols significantly enhanced the efficacy of statin mediated cell death. (ucc.ie)
- In a recent article in the Journal of Lipid Research, a research team led by X. Charlie Dong at Indiana University School of Medicine reported that Sirt6 plays a critical role in the regulation of SREBP-2. (asbmb.org)
- Among its related pathways are Regulation of cholesterol biosynthesis by SREBP (SREBF) and wtCFTR and delta508-CFTR traffic / Generic schema (norm and CF) . An important paralog of this gene is SEC24C . (genecards.org)
- Indeed, upregulated hepatic SREBP-1c mRNA expression has been observed in obese mice and humans ( 8 , 9 ), although its molecular determinants remain largely unknown. (diabetesjournals.org)
- Conversely, polyunsaturated fatty acids (PUFAs), such as eicosapentaenoate (EPA), have been shown to inhibit hepatic SREBP-1c through multiple mechanisms ( 22 , 23 ). (diabetesjournals.org)
- In addition, the role of SREBP‑2 function in cholesterol synthesis from the gerbil primary hepatic cells was also investigated by modulation of SERBP‑2 expression via the transfection of SREBP‑2 overexpression and knockdown plasmids, respectively. (spandidos-publications.com)
- This study demonstrated that AST attenuates IR and lipid accumulation in HepG2 cells by regulating AMPK-dependent phosphorylation of SREBP-1c at Ser372, suggesting AST as a promising drug for treating hepatic steatosis. (frontiersin.org)
- As a logical extension of our ongoing studies we now propose to examine the molecular mechanisms by which polyunsaturated fatty acids (PUFA), specifically n-3 PUFA, reduce transcription of SREBP-1c, thereby effectively mitigating the effect of insulin to induce lipogenic enzyme expression and hepatic lipid overproduction in hyperinsulinemic states. (labome.org)
- Furthermore, in diet-induced obese mice, dietary XN suppressed SREBP-1 target gene expression in the liver accompanied by a reduction of the mature form of hepatic SREBP-1, and it inhibited the development of obesity and hepatic steatosis. (pubmedcentralcanada.ca)
- Compared with the control, BF175 treatment decreased the expression of SREBP target genes in mouse livers and decreased hepatic and blood levels of lipids. (elsevier.com)
- PAQR3 knockdown in liver blunts SREBP pathway and decreases hepatic cholesterol content. (antibodychain.com)
- The development of insulin resistance and fatty liver in obese cows was paralleled by increased hepatic expression of the IR beta, CD36 and SREBP-1. (ac.rs)
- These results suggest that increased expression of hepatic CD36 and SREBP-1 is relevant in the obesity-driven lipid accumulation in the liver of dairy cows during late gestation. (ac.rs)
- These findings were validated by showing that CR failed to upregulate factors involved in FA biosynthesis and to extend longevity in SREBP-1c knockout mice. (mdpi.com)
- We conclude that CR induces SREBP-1c-dependent metabolic remodeling, including the enhancement of FA biosynthesis and mitochondrial activation, via PGC-1α in WAT, resulting in beneficial effects. (mdpi.com)
- found that neuregulin 1 (NRG1)-mediated activation of the EGFR member ERBB4 stimulated the transcription factor SREBP-2, which enhanced the expression of the receptor needed to uptake cholesterol-rich low-density lipoproteins and genes involved in cholesterol biosynthesis in cultured breast epithelial cells. (sciencemag.org)
- Expression of the ERBB4 ICD in mammary epithelial cells or activation of ERBB4 with the ligand neuregulin 1 (NRG1) induced the expression of SREBP target genes involved in cholesterol biosynthesis, including HMGCR and HMGCS1 , and lipid uptake, LDLR , which encodes the LDL receptor. (sciencemag.org)
- Pharmacological inhibition of the activity of SREBP site 1 protease or of all EGFR family members (with lapatinib), but not EGFR alone (with erlotinib), impaired NRG1-induced expression of cholesterol biosynthesis genes. (sciencemag.org)
- Thus, we conclude that the fungal SREBP, SrbA, is critical for coordinating genes involved in iron acquisition and ergosterol biosynthesis under hypoxia and low iron conditions found at sites of human fungal infections. (prolekare.cz)
- The SREBP (sterol response element binding proteins) transcription factors are central to regulating de novo biosynthesis of cholesterol and fatty acids. (ucc.ie)
- INSIG1 has a central role in regulating SREBP processing and in regulating stability of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate limiting enzyme in cholesterol biosynthesis. (ucc.ie)
- SREBP maintains lipid biosynthesis and viability of cancer cells under lipid- and oxygen-deprived conditions and defines a gene signature associated with poor survival in glioblastoma multiforme. (ox.ac.uk)
- Inhibition of SREBP function blocked lipid biosynthesis in hypoxic cancer cells and impaired cell survival under hypoxia and in a three-dimensional spheroid model. (ox.ac.uk)
- Thus, PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis. (antibodychain.com)
- SREBP-2 is crucial in cholesterol metabolism, and it is a major regulator of the cholesterol biosynthesis enzyme HMGCR. (edu.hk)
- The SREBP precursors are activated by a two-step cleavage process that releases the active form that then translocates to the nucleus of the cell to stimulate gene expression [ 13 ]. (pubmedcentralcanada.ca)
- Finally, gene expression analysis revealed that SREBP defines a gene signature that is associated with poor survival in glioblastoma. (ox.ac.uk)
- Among these novel compounds, BF175 can speci fi cally block the binding of MED15-KIX to SREBP1a-TAD in vitro, resulting in an inhibition of the SREBP transcriptional activity and a decrease of SREBP target gene expression in cultured hepatocytes. (elsevier.com)
- C-E Expression profile of miR-33a/b and SREBP host genes in selected human tissues. (nih.gov)
- While SREBP-1 is thought to be more important in regulating the expression of genes involved in triglyceride synthesis and accumulation, SREBP-2 has been more closely linked to those involved in cholesterol synthesis and accumulation. (thermofisher.com)
- Expression of SREBP-1c is highly upregulated by dietary intake of carbohydrates and sugars ( 18 - 21 ). (diabetesjournals.org)
- The overexpression of Insig-1 significantly inhibits SREBP-1c expression and thereby blocks the expression of downstream genes. (spandidos-publications.com)
- It has been demonstrated that the upregulation of Insig-1 decreases SREBP-1c expression, thereby inhibiting lipid synthesis ( 8 ). (spandidos-publications.com)
- In our previous study, we demonstrated that the overexpression of Insig-1 leads to the inhibition of SREBP-1c expression and the subsequent improvement of β cell function ( 9 ). (spandidos-publications.com)
- Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg/L ox-lipid density lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. (nih.gov)
- Lipid-loaded VSMC exposed to N-acetyl- Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear translocation of SREBP-1, reduced caveolin-1 expression level, and upregulated cellular lipid levels. (nih.gov)
- Curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1. (nih.gov)
- Here we used Western blot analysis to examine the impact of gestation and 0.2% ECD on the expression levels of fatty acid synthase (FAS), HMGR and SREBP-1/2, which are involved in either lipid or cholesterol synthesis. (biomedsearch.com)
- SREBP-1a and -1c mainly activate the expression of genes involved in fatty acid synthesis, whereas SREBP-2 preferentially stimulates the expression of genes involved in cholesterol synthesis. (pubmedcentralcanada.ca)
- Surprisingly, we found that elimination of Srebf-2 in hepatocytes of mice also markedly reduced SREBP-1c and the expression of all genes involved in FA and triglyceride synthesis that are normally regulated by SREBP-1c. (elifesciences.org)
- The deletion of Srebf-2 and subsequent lower sterol synthesis in hepatocytes eliminated the production of an endogenous sterol ligand required for LXR activity and SREBP-1c expression. (elifesciences.org)
- These studies demonstrate that cholesterol and FA synthesis in hepatocytes are coupled and that flux through the cholesterol biosynthetic pathway is required for the maximal SREBP-1c expression and high rates of FA synthesis. (elifesciences.org)
- We previously demonstrated that exogenous expression of Rev-erb betaDeltaE in skeletal muscle cells increased Srebp-1c mRNA expression. (garvan.org.au)
- We validated these in vitro observations by injection of an expression vector driving Rev-erb betaDeltaE expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. (garvan.org.au)
- Paradoxically, Rev-erb beta siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb beta expression was necessary for Srebp-1c expression. (garvan.org.au)
- and (ii) increased Rev-erb beta and Srebp-1c mRNA expression. (garvan.org.au)
- Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). (inserm.fr)
- There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. (biomedcentral.com)
- We found that SREBP transcriptional activity was induced by serum depletion both in normoxic and hypoxic cells and that activation of SREBP was required to maintain the expression of fatty acid and cholesterol metabolism genes under hypoxic conditions. (ox.ac.uk)
- Accordingly, in an SREBP-2 active condition antisense-mediated inhibition of miR-33a-3p, but not miR-33a-5p, led to decreased LDLR expression and LDL uptake in human hepatocytes. (qscience.com)
- Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. (elsevier.com)
- SREBP-1 expression produces two different isoforms, SREBP-1a and -1c. (wikipedia.org)
- The data provided the first line of the evidence that BBR, similar to the Sim, could increase the expression of PCSK9 levels in HFD rats through SREBP-2 activation, suggesting that impacts of BBR on lipid profile may also be linked to SREBP-2 pathway. (biomedcentral.com)
- We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic profile as key characteristic features of metastatic Pml and Pten double-null CaP. (nature.com)
- Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes. (wikipathways.org)
- This domain responds to sterols by causing the SCAP.SREBP complex to be retained in the ER, preventing proteolytic release and reducing transcription of lipogenic genes. (eurekamag.com)
- Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN). (wikipathways.org)
- We are examining the ability of highly unsaturated fatty acids (Polyunsaturated Fatty Acids or PUFA) derived from fish oil to reduce fat production in the liver by decreasing levels of SREBP-1c. (labome.org)
- Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARalpha and SREBP-1c signaling. (biomedsearch.com)
- Effect of an enriched cholesterol diet during gestation on fatty acid synthase, HMG-CoA reductase and SREBP-1/2 expressions in rabbits. (biomedsearch.com)
- Here, we demonstrate that a prenylated flavonoid in hops, xanthohumol (XN), is a novel SREBP inactivator that reduces the de novo synthesis of fatty acid and cholesterol. (pubmedcentralcanada.ca)
- The synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 and SREBP-1c, respectively. (elifesciences.org)
- Fig. 5: SREBP is the downstream target of PML -loss-induced MAPK activation. (nature.com)
- Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex. (nih.gov)
- Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. (mdpi.com)
- Thus, inhibition of SREBP activation is a potential therapeutic approach to treating metabolic disorders. (rsc.org)
- This review focuses on direct or indirect small-molecule inhibitors of SREBP activation. (rsc.org)
- These results indicated that the activation of SREBP‑2 to HMGCR was not terminated in gerbil livers during cholesterol intake. (spandidos-publications.com)
- SREBP-1 Activation by Glucose Mediates TGFخ² Upregulation in Mesangial Cells. (wikipathways.org)
- Collectively, our findings indicated that activation of ERBB4 promotes SREBP-2-regulated cholesterol metabolism. (sciencemag.org)
- SSW causes dephosphorylation/ inactivation of AMPK, which contributes to increased activation of SREBP-1. (pubmedcentralcanada.ca)
- Kartawijaya M, Han H, Kim Y, Lee S-M. Genistein upregulates LDLR levels via JNK-mediated activation of SREBP-2. (foodandnutritionresearch.net)
- SREBP activation by proteolytic cleavage. (wikipedia.org)
- Disrupting the interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP processing and activation. (antibodychain.com)
- MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. (nih.gov)
- Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases. (nih.gov)
- SREBP transcription factors: master regulators of lipid homeostasis. (wikipathways.org)
- An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. (wikipathways.org)
- These results suggest that blocking the interaction between SREBP-TADs and the Mediator complex by small molecules may represent a novel approach for treating diseases with aberrant lipid homeostasis. (elsevier.com)
- SREBPs are encoded by two distinct genes, SREBP-1 and SREBP-2. (mdpi.com)
- These vesicles then transport the SCAP/SREBP complex from the ER to the Golgi, wherein two proteases, site-1 protease (S1P) and site-2 protease (S2P), sequentially cleave SREBPs ( 5 , 6 ). (pubmedcentralcanada.ca)
- When cellular sterol levels are sufficient, SCAP associates with insulin-induced genes (Insigs), which facilitate the retention of the SCAP/SREBP complex in the ER, suppressing the proteolytic processing of SREBPs ( 7 ). (pubmedcentralcanada.ca)
- To generate the active nuclear form of SREBPs, SREBP/Scap dissociates from Insig, and the complex moves from the ER to the Golgi where two proteases, designated S1P and S2P, sequentially cleave SREBPs releasing the amino-terminal fragment, which travels to the nucleus to activate regulated genes. (elifesciences.org)
- The three isoforms of SREBP precursors located on the endoplasmic reticulum membrane, designated SREBP-1a, SREBP-1c, and SREBP-2 [ 12 ], have different functions and abundance in various animal tissues. (pubmedcentralcanada.ca)
- There are three major SREBP isoforms in mammals, SREBP-1a, -1c, and -2 ( 8 ). (pubmedcentralcanada.ca)
- These isoforms differ in their first exons owing to the use of different transcriptional start sites for the SREBP-1 gene. (wikipedia.org)
- Suppression of IRS-2/Akt pathway could be a part of the downstream mechanism for the SREBP-1c-mediated insulin secretion defect because adenoviral constitutively active Akt compensated it. (diabetesjournals.org)
- In this study, we further explored the downstream effects of silibinin on the Insig-1/SREBP-1c pathway, which may be a novel target in the protection of β cells against glucotoxicity. (spandidos-publications.com)
Scap dissociates from Insig1
- AST also inhibited translocation of SREBP-1c into the nucleus of insulin-resistant HepG2 cells by inducing phosphorylation of SREBP-1c at Ser372. (frontiersin.org)
- the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. (nih.gov)
- Our lab has previously illustrated that apigenin and luteolin could attenuate the nuclear translocation of SREBP-2 through an AMPK-dependent pathway. (edu.hk)
- At the molecular level, we show that Sox4 could directly control the transcription of SREBP-1c gene through binding to its proximal promoter region. (diabetesjournals.org)
- Specifically, we have been studying the insulin-responsive cis-acting elements of the rat SREBP-1c promoter and have found that its full response requires participation of multiple cis-acting sites that bind to LXR1, NF-Y, Sp1 and SREBP-1c itself. (labome.org)
- Genistein increased the nuclear fraction of SREBP-2 and the DNA-binding activity of SREBP-2 to LDLR promoter, as assessed by CHIP. (foodandnutritionresearch.net)
- ChIP analysis demonstrated that Rev-erb beta was recruited to the Srebp-1c promoter. (garvan.org.au)
- Moreover, Rev-erb beta trans-activated the Srebp-1c promoter, in contrast, Rev-erb beta efficiently repressed the Rev-erb alpha promoter, a previously characterized target gene. (garvan.org.au)
- Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. (mybiosource.com)
- Importantly, a high-fat diet (HFD) induced lipid accumulation in prostate tumors and was sufficient to drive metastasis in a nonmetastatic Pten -null mouse model of CaP, and an SREBP signature was highly enriched in metastatic human CaP. (nature.com)
- We have demonstrated that mTORC1 stimulates the accumulation of processed, active SREBP, although details of the molecular mechanism remain to be elucidated. (harvard.edu)
- Astragaloside IV (AST-IV) was found to decrease lipid accumulation in hepatocytes by activating AMPK, which is required to regulate lipid metabolism in liver tissue by inducing SREBP-1c phosphorylation. (frontiersin.org)
- Also, it binds SREBP by a series of consecutive WD repeats on its C-terminus. (wikipedia.org)
- The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. (nih.gov)
- Specific proteases digest the precursor to generate a 65 kd form of SREBP (nSREBP) that travels to the nucleus where it binds SREs. (nap.edu)
Site 1 protea1
Inhibition of SREBP2
- Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. (nih.gov)
- On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. (antibodychain.com)
- These palmitate-EPA effects on insulin secretion were abolished in SREBP-1-null islets. (diabetesjournals.org)
- CONCLUSIONS- SREBP-1c plays a dominant role in palmitate-mediated insulin secretion defect, and EPA prevents it through SREBP-1c inhibition, implicating a therapeutic potential for treating diabetes related to lipotoxicity. (diabetesjournals.org)
- Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. (wikipathways.org)
- Insulin induced gene-1 (Insig-1) is an upstream regulatory factor of SREBP-1c. (spandidos-publications.com)
- We obtained in silico and mass spectrometry evidence, that was combined with siRNA strategies, to discover that insulin-induced phosphorylation of serine 418, serine 419, and serine 422 in rat SREBP-1c was most likely mediated by p70S6 kinase. (elsevier.com)
- Here, for the first time, we show that insulin-induced phosphorylation of these 3 serine residues mainly impinged on the mechanisms of proteostasis of both full-length and mature SREBP-1c in the McArdle-RH7777 hepatoma cells. (elsevier.com)
- Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE −/− Mice Fed with a High-Fat Diet," Evidence-Based Complementary and Alternative Medicine , vol. 2017, Article ID 3121989, 8 pages, 2017. (hindawi.com)
- The results indicated that the combination of CGA and caffeine had anti-obesity effects and regulated lipid metabolism in high-fat diet-induced obese mice via the AMPKα-LXRα/SREBP-1c signaling pathway. (rsc.org)
- Engelking, LJ , Cantoria, MJ, Xu, Y & Liang, G 2017, ' Developmental and extrahepatic physiological functions of SREBP pathway genes in mice ', Seminars in Cell and Developmental Biology . (elsevier.com)
- We also investigated whether phosphorylation of SREBP-1c at Ser372 was required for AST function. (frontiersin.org)
- The CGA and caffeine combination also promoted the phosphorylation of AMPKα, inhibited the expressions of transcriptional regulators (SREBP-1c and LXRα), and decreased the expressions of FAS and HMGR. (rsc.org)
- The antiserum was produced against synthesized non-phosphopeptide derived from human SREBP-1 around the phosphorylation site of serine 439 (Q-S-SP-P-L). (mybiosource.com)
- These studies provide a potential mechanistic explanation for the ability of sterols to block SCAP.SREBP movement from the ER and thereby to control lipid synthesis in animal cells. (eurekamag.com)
- Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is rapidly catabolized, thereby reducing transcription. (elsevier.com)
- The Akt-SREBP nexus: cell signaling meets lipid metabolism. (wikipathways.org)
- The connections of EGFR and ERBB4 signaling with SREBP-2-regulated cholesterol metabolism are likely to be important in ERBB-regulated developmental processes and may contribute to metabolic remodeling in ERBB-driven cancers. (sciencemag.org)
- We found that microRNA 33a (miR-33a) embedded within the intronic sequence of SREBP-2 gene, the master regulator of cholesterol metabolism, acts as a key modulator of intracellular cholesterol trafficking pathways. (qscience.com)
- These changes in cholesterol metabolism are due, at least in part, to the effect of cholesterol on the nuclear content of a family of specific transcription factors called sterol regulatory element binding proteins (SREBP). (nap.edu)
Membrane-bound transcription factor1
- Consistent with this conclusion, nascent SREBP-1c, substituted with phosphomimetic aspartic acid residues at these 3 sites, was resistant to proteasomal degradation. (elsevier.com)
- Remarkably, aspartic acid substitutions at S418, S419 and S422 also protected the nascent SREBP-1c from ubiquitin-mediated proteasome degradation thus increasing its steady-state levels and transactivation potential in the nucleus. (elsevier.com)
- Our data unravels a novel regulatory circuit by which LDLR, which is transcriptionally activated by SREBP-2, is further protected from degradation at the post-translational level by miR-33a-3p. (qscience.com)
- MG stabilizing properties are shared by some NSC 131463 of its synthetic Rabbit Polyclonal to SREBP-1 (phospho-Ser439) derivatives like mannosyl lactate (ML). In turn, diglycerol phosphate (DGP) is certainly a fresh and uncommon hypersolute from Archaeoglogus and it shows exceptional properties of proteins stabilization [11, (healthandwellnesssource.org)
- Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. (antibodychain.com)