Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.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.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.Sp1 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.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.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Basic Helix-Loop-Helix Transcription Factors: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.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.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.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.Transcription Factor AP-1: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.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.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.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).Basic-Leucine Zipper Transcription Factors: A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.Transcription Factor AP-2: A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.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.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)Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Kruppel-Like Transcription Factors: A family of zinc finger transcription factors that share homology with Kruppel protein, Drosophila. They contain a highly conserved seven amino acid spacer sequence in between their ZINC FINGER MOTIFS.Transcription Factors, TFII: The so-called general transcription factors that bind to RNA POLYMERASE II and that are required to initiate transcription. They include TFIIA; TFIIB; TFIID; TFIIE; TFIIF; TFIIH; TFII-I; and TFIIJ. In vivo they apparently bind in an ordered multi-step process and/or may form a large preinitiation complex called RNA polymerase II holoenzyme.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.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.YY1 Transcription Factor: A ubiquitously expressed zinc finger-containing protein that acts both as a repressor and activator of transcription. It interacts with key regulatory proteins such as TATA-BINDING PROTEIN; TFIIB; and ADENOVIRUS E1A PROTEINS.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.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.GATA4 Transcription Factor: A GATA transcription factor that is expressed in the MYOCARDIUM of developing heart and has been implicated in the differentiation of CARDIAC MYOCYTES. GATA4 is activated by PHOSPHORYLATION and regulates transcription of cardiac-specific genes.Transcription Factor TFIID: The major sequence-specific DNA-binding component involved in the activation of transcription of RNA POLYMERASE II. It was originally described as a complex of TATA-BOX BINDING PROTEIN and TATA-BINDING PROTEIN ASSOCIATED FACTORS. It is now know that TATA BOX BINDING PROTEIN-LIKE PROTEINS may take the place of TATA-box binding protein in the complex.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.Activating Transcription Factor 3: An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.NFATC Transcription Factors: A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.Sp3 Transcription Factor: A specificity protein transcription factor that regulates expression of a variety of genes including VASCULAR ENDOTHELIAL GROWTH FACTOR and CYCLIN-DEPENDENT KINASE INHIBITOR P27.Transcription Initiation Site: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.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.Zinc Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.Paired Box Transcription Factors: A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.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.Activating Transcription Factor 2: An activating transcription factor that regulates expression of a variety of GENES including C-JUN GENES; CYCLIN A; CYCLIN D1; and ACTIVATING TRANSCRIPTION FACTOR 3.Transcription Factor TFIIB: An RNA POLYMERASE II specific transcription factor. It plays a role in assembly of the pol II transcriptional preinitiation complex and has been implicated as a target of gene-specific transcriptional activators.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.E2F1 Transcription Factor: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.RNA Polymerase II: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 22.214.171.124.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.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.Basic Helix-Loop-Helix Leucine Zipper Transcription Factors: A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.MEF2 Transcription Factors: Activating transcription factors of the MADS family which bind a specific sequence element (MEF2 element) in many muscle-specific genes and are involved in skeletal and cardiac myogenesis, neuronal differentiation and survival/apoptosis.Recombinant 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.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.GATA3 Transcription Factor: A GATA transcription factor that is found predominately in LYMPHOID CELL precursors and has been implicated in the CELL DIFFERENTIATION of HELPER T-CELLS. Haploinsufficiency of GATA3 is associated with HYPOPARATHYROIDISM; SENSORINEURAL HEARING LOSS; and renal anomalies syndrome.GATA1 Transcription Factor: A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.GATA2 Transcription Factor: An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.TCF Transcription Factors: A family of DNA-binding proteins that are primarily expressed in T-LYMPHOCYTES. They interact with BETA CATENIN and serve as transcriptional activators and repressors in a variety of developmental processes.GATA Transcription Factors: A family of transcription factors that contain two ZINC FINGER MOTIFS and bind to the DNA sequence (A/T)GATA(A/G).Microphthalmia-Associated Transcription Factor: A basic helix-loop-helix leucine zipper transcription factor that regulates the CELL DIFFERENTIATION and development of a variety of cell types including MELANOCYTES; OSTEOCLASTS; and RETINAL PIGMENT EPITHELIUM. Mutations in MITF protein have been associated with OSTEOPETROSIS and WAARDENBURG SYNDROME.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.STAT1 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.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.Activating Transcription Factors: Activating transcription factors were originally identified as DNA-BINDING PROTEINS that interact with early promoters from ADENOVIRUSES. They are a family of basic leucine zipper transcription factors that bind to the consensus site TGACGTCA of the cyclic AMP response element, and are closely related to CYCLIC AMP-RESPONSIVE DNA-BINDING PROTEIN.Transcription Factor RelA: A subunit of NF-kappa B that is primarily responsible for its transactivation function. It contains a C-terminal transactivation domain and an N-terminal domain with homology to PROTO-ONCOGENE PROTEINS C-REL.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.Cell Line, Tumor: A cell line derived from cultured tumor cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.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.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. 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.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.GATA6 Transcription Factor: A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and regulates vascular smooth muscle CELL DIFFERENTIATION.Activating Transcription Factor 4: An activating transcription factor that regulates the expression of a variety of GENES involved in amino acid metabolism and transport. It also interacts with HTLV-I transactivator protein.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.Transcription Factor 7-Like 1 Protein: A transcription factor that takes part in WNT signaling pathway where it may play a role in the differentiation of KERATINOCYTES. The transcriptional activity of this protein is regulated via its interaction with BETA CATENIN.Activating Transcription Factor 1: An activating transcription factor that regulates expression of a variety of genes including C-JUN GENES and TRANSFORMING GROWTH FACTOR BETA2.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.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.Transcription Factor TFIIIA: One of several general transcription factors that are specific for RNA POLYMERASE III. It is a zinc finger (ZINC FINGERS) protein and is required for transcription of 5S ribosomal genes.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.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.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.TATA Box: A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.NFI Transcription Factors: Transcription factors that were originally identified as site-specific DNA-binding proteins essential for DNA REPLICATION by ADENOVIRUSES. They play important roles in MAMMARY GLAND function and development.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.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.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.Proto-Oncogene Proteins c-jun: Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Proto-Oncogene Proteins c-ets: A family of transcription factors that share a unique DNA-binding domain. The name derives from viral oncogene-derived protein oncogene protein v-ets of the AVIAN ERYTHROBLASTOSIS VIRUS.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Transcription Factor TFIIH: A general transcription factor that is involved in basal GENETIC TRANSCRIPTION and NUCLEOTIDE EXCISION REPAIR. It consists of nine subunits including ATP-DEPENDENT DNA HELICASES; CYCLIN H; and XERODERMA PIGMENTOSUM GROUP D PROTEIN.Mice, Inbred C57BLSOX9 Transcription Factor: A SOXE transcription factor that plays a critical role in regulating CHONDROGENESIS; OSTEOGENESIS; and male sex determination. Loss of function of the SOX9 transcription factor due to genetic mutations is a cause of CAMPOMELIC DYSPLASIA.Transcription Factor TFIIA: An RNA POLYMERASE II specific transcription factor. It may play a role in transcriptional activation of gene expression by interacting with the TATA-BOX BINDING PROTEIN component of TRANSCRIPTION FACTOR TFIID.DNA-Directed RNA Polymerases: Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.STAT5 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.Transcription Factor DP1: A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.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)Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.T-Box Domain Proteins: Proteins containing a region of conserved sequence, about 200 amino acids long, which encodes a particular sequence specific DNA binding domain (the T-box domain). These proteins are transcription factors that control developmental pathways. The prototype of this family is the mouse Brachyury (or T) gene product.Fungal Proteins: Proteins found in any species of fungus.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.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.Octamer Transcription Factor-1: A ubiquitously expressed octamer transcription factor that regulates GENETIC TRANSCRIPTION of SMALL NUCLEAR RNA; IMMUNOGLOBULIN GENES; and HISTONE H2B genes.Regulatory Elements, Transcriptional: Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.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.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.TATA-Box Binding Protein: A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.Erythroid-Specific DNA-Binding Factors: A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.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.Transcription Factors, TFIII: Factors that bind to RNA POLYMERASE III and aid in transcription. They include the assembly factors TFIIIA and TFIIIC and the initiation factor TFIIIB. All combine to form a preinitiation complex at the promotor that directs the binding of RNA POLYMERASE III.GA-Binding Protein Transcription Factor: A heterotetrameric transcription factor composed of two distinct proteins. Its name refers to the fact it binds to DNA sequences rich in GUANINE and ADENINE. GA-binding protein integrates a variety of SIGNAL TRANSDUCTION PATHWAYS and regulates expression of GENES involved in CELL CYCLE control, PROTEIN BIOSYNTHESIS, and cellular METABOLISM.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Gene Regulatory Networks: Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.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.Early Growth Response Protein 1: An early growth response transcription factor that has been implicated in regulation of CELL PROLIFERATION and APOPTOSIS.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.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.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.High Mobility Group Proteins: A family of low-molecular weight, non-histone proteins found in chromatin.Bacterial Proteins: Proteins found in any species of bacterium.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Transcription Factor 7-Like 2 Protein: A transcription factor that takes part in WNT signaling pathway. The activity of the protein is regulated via its interaction with BETA CATENIN. Transcription factor 7-like 2 protein plays an important role in the embryogenesis of the PANCREAS and ISLET CELLS.Proto-Oncogene Protein c-ets-1: An ets proto-oncogene expressed primarily in adult LYMPHOID TISSUE; BRAIN; and VASCULAR ENDOTHELIAL CELLS.Deoxyribonuclease I: An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.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)Reverse Transcription: The biosynthesis of DNA carried out on a template of RNA.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Twist Transcription Factor: A basic helix-loop-helix transcription factor that was originally identified in DROSOPHILA as essential for proper gastrulation and MESODERM formation. It plays an important role in EMBRYONIC DEVELOPMENT and CELL DIFFERENTIATION of MUSCLE CELLS, and is found in a wide variety of organisms.NF-E2 Transcription Factor, p45 Subunit: A tissue-specific subunit of NF-E2 transcription factor that interacts with small MAF PROTEINS to regulate gene expression. P45 NF-E2 protein is expressed primarily in MEGAKARYOCYTES; ERYTHROID CELLS; and MAST CELLS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Chloramphenicol O-Acetyltransferase: An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 126.96.36.199.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.Proto-Oncogene Proteins c-fos: Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Nerve Tissue ProteinsOligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Transcription Factor TFIIIB: One of several general transcription factors that are specific for RNA POLYMERASE III. TFIIIB recruits and positions pol III over the initiation site and remains stably bound to the DNA through multiple rounds of re-initiation by RNA POLYMERASE III.Active Transport, Cell Nucleus: Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.Activating Transcription Factor 6: One of the BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS that is synthesized as a membrane-bound protein in the ENDOPLASMIC RETICULUM. In response to endoplasmic reticulum stress it translocates to the GOLGI APPARATUS. It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the unfolded protein response.Transcription Factor Brn-3: A family of mammalian POU domain factors that are expressed predominately in NEURONS.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.SOXB1 Transcription Factors: A subclass of SOX transcription factors that are expressed in neuronal tissue where they may play a role in the regulation of CELL DIFFERENTIATION. Members of this subclass are generally considered to be transcriptional activators.Acetylation: Formation of an acetyl derivative. (Stedman, 25th 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.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).)NF-E2 Transcription Factor: A basic-leucine zipper transcription factor that regulates GLOBIN gene expression and is related to TRANSCRIPTION FACTOR AP-1. NF-E2 consists of a small MAF protein subunit and a tissue-restricted 45 kDa subunit.Genes, Regulator: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.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.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.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.SOXE Transcription Factors: A subclass of closely-related SOX transcription factors. Members of this subfamily have been implicated in regulating the differentiation of OLIGODENDROCYTES during neural crest formation and in CHONDROGENESIS.Upstream Stimulatory Factors: Ubiquitously expressed basic HELIX-LOOP-HELIX MOTIF transcription factors. They bind CANNTG sequences in the promoters of a variety of GENES involved in carbohydrate and lipid metabolism.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Myogenic Regulatory Factors: A family of muscle-specific transcription factors which bind to DNA in control regions and thus regulate myogenesis. All members of this family contain a conserved helix-loop-helix motif which is homologous to the myc family proteins. These factors are only found in skeletal muscle. Members include the myoD protein (MYOD PROTEIN); MYOGENIN; myf-5, and myf-6 (also called MRF4 or herculin).RNA Polymerase III: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure where it transcribes DNA into RNA. It has specific requirements for cations and salt and has shown an intermediate sensitivity to alpha-amanitin in comparison to RNA polymerase I and II. EC 188.8.131.52.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Pol1 Transcription Initiation Complex Proteins: Factors that form a preinitiation complex at promoters that are specifically transcribed by RNA POLYMERASE I.Transcription Factor 3: A basic helix-loop-helix transcription factor that plays a role in determining cell fate during embryogenesis. It forms a heterodimer with TWIST TRANSCRIPTION FACTOR and ACHAETE-SCUTE GENE COMPLEX-related TRANSCRIPTION FACTORS.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.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.Transcription Factor Pit-1: A POU domain factor that regulates expression of GROWTH HORMONE; PROLACTIN; and THYROTROPIN-BETA in the ANTERIOR PITUITARY GLAND.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Dominant negative murine serum response factor: alternative splicing within the activation domain inhibits transactivation of serum response factor binding targets. (1/241)Primary transcripts encoding the MADS box superfamily of proteins, such as MEF2 in animals and ZEMa in plants, are alternatively spliced, producing several isoformic species. We show here that murine serum response factor (SRF) primary RNA transcripts are alternatively spliced at the fifth exon, deleting approximately one-third of the C-terminal activation domain. Among the different muscle types examined, visceral smooth muscles have a very low ratio of SRFDelta5 to SRF. Increased levels of SRFDelta5 correlates well with reduced smooth muscle contractile gene activity within the elastic aortic arch, suggesting important biological roles for differential expression of SRFDelta5 variant relative to wild-type SRF. SRFDelta5 forms DNA binding-competent homodimers and heterodimers. SRFDelta5 acts as a naturally occurring dominant negative regulatory mutant that blocks SRF-dependent skeletal alpha-actin, cardiac alpha-actin, smooth alpha-actin, SM22alpha, and SRF promoter-luciferase reporter activities. Expression of SRFDelta5 interferes with differentiation of myogenic C2C12 cells and the appearance of skeletal alpha-actin and myogenin mRNAs. SRFDelta5 repressed the serum-induced activity of the c-fos serum response element. SRFDelta5 fused to the yeast Gal4 DNA binding domain displayed low transcriptional activity, which was complemented by overexpression of the coactivator ATF6. These results indicate that the absence of exon 5 might be bypassed through recruitment of transcription factors that interact with extra-exon 5 regions in the transcriptional activating domain. The novel alternatively spliced isoform of SRF, SRFDelta5, may play an important regulatory role in modulating SRF-dependent gene expression. (+info)
Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. (2/241)The unfolded protein response (UPR) controls the levels of molecular chaperones and enzymes involved in protein folding in the endoplasmic reticulum (ER). We recently isolated ATF6 as a candidate for mammalian UPR-specific transcription factor. We report here that ATF6 constitutively expressed as a 90-kDa protein (p90ATF6) is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed cells. Furthermore, we showed that the most important consequence of this conversion was altered subcellular localization; p90ATF6 is embedded in the ER, whereas p50ATF6 is a nuclear protein. p90ATF6 is a type II transmembrane glycoprotein with a hydrophobic stretch in the middle of the molecule. Thus, the N-terminal half containing a basic leucine zipper motif is oriented facing the cytoplasm. Full-length ATF6 as well as its C-terminal deletion mutant carrying the transmembrane domain is localized in the ER when transfected. In contrast, mutant ATF6 representing the cytoplasmic region translocates into the nucleus and activates transcription of the endogenous GRP78/BiP gene. We propose that ER stress-induced proteolysis of membrane-bound p90ATF6 releases soluble p50ATF6, leading to induced transcription in the nucleus. Unlike yeast UPR, mammalian UPR appears to use a system similar to that reported for cholesterol homeostasis. (+info)
Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. (3/241)ATF6 is a member of the basic-leucine zipper family of transcription factors. It contains a transmembrane domain and is located in membranes of the endoplasmic reticulum. ATF6 has been implicated in the endoplasmic reticulum (ER) stress response pathway since it can activate expression of GRP78 and other genes induced by the ER stress response. ER stress appears to activate ATF6 by cleavage from the ER membrane and translocation to the nucleus. However, direct DNA binding by ATF6 had not been demonstrated. In this report, we have identified a consensus DNA binding sequence for ATF6. This site is related to but distinct from ATF1/CREB binding sites. The site was placed in a reporter gene and was specifically activated by ATF6 overexpression and was strongly induced by the ER stress response. A dominant negative form of ATF6 blocked ER stress induction of both ATF6 site and GRP78 reporter genes. We further found that GAL4-ATF6 could be activated by ER stress. These results demonstrate that ATF6 is a direct target of the ER stress response. A proximal sensor of the ER stress response, human IRE1 (hIRE1), was sufficient to activate the ATF6 reporter gene, while a dominant negative form of hIRE1 blocked ER stress activation, suggesting that hIRE1 is upstream of ATF6 in the ER stress signaling pathway. (+info)
ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1. (4/241)ATF6, a member of the leucine zipper protein family, can constitutively induce the promoter of glucose-regulated protein (grp) genes through activation of the endoplasmic reticulum (ER) stress element (ERSE). To understand the mechanism of grp78 induction by ATF6 in cells subjected to ER calcium depletion stress mediated by thapsigargin (Tg) treatment, we discovered that ATF6 itself undergoes Tg stress-induced changes. In nonstressed cells, ATF6, which contains a putative short transmembrane domain, is primarily associated with the perinuclear region. Upon Tg stress, the ATF6 protein level dropped initially but quickly recovered with the additional appearance of a faster-migrating form. This new form of ATF6 was recovered as soluble nuclear protein by biochemical fractionation, correlating with enhanced nuclear localization of ATF6 as revealed by immunofluorescence. Optimal ATF6 stimulation requires at least two copies of the ERSE and the integrity of the tripartite structure of the ERSE. Of primary importance is a functional NF-Y complex and a high-affinity NF-Y binding site that confers selectivity among different ERSEs for ATF6 inducibility. In addition, we showed that YY1 interacts with ATF6 and in Tg-treated cells can enhance ATF6 activity. The ERSE stimulatory activity of ATF6 exhibits properties distinct from those of human Ire1p, an upstream regulator of the mammalian unfolded protein response. The requirement for a high-affinity NF-Y site for ATF6 but not human Ire1p activity suggests that they stimulate the ERSE through diverse pathways. (+info)
ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. (5/241)Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by the cis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N(9)-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1. (+info)
Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response. (6/241)Herp is a 54-kDa membrane protein in the endoplasmic reticulum (ER). The mRNA expression level of Herp is increased by the accumulation of unfolded proteins in the ER. Transcriptional changes designed to deal with this type of ER stress is called the unfolded protein response (UPR). Most mammalian UPR-target genes encode ER-resident molecular chaperones: GRP78, GRP94, and calreticulin. The promoter regions of these genes contain a cis-acting ER stress response element, ERSE, with the consensus sequence of CCAAT-N(9)-CCACG. Under conditions of ER stress, p50ATF6 (the active form of the transcription factor, ATF6) binds to CCACG when CCAAT is bound by the general transcription factor, NF-Y/CBF. Here, we report the genomic structure of human Herp and the presence of a new ER stress response element, ERSE-II, in its promoter region. The gene for Herp consists of eight exons, localized to chromosome 16q12.2-13. The promoter region contains a single ERSE-like sequence. In reporter gene assays, disruption of this cis-element resulted in a partial reduction of the transcriptional response to ER stress, suggesting that the element is functional for the UPR. These results also suggest the involvement of additional elements in the UPR. Further analysis, using an optimized plasmid containing an mRNA-destabilizing sequence, revealed ERSE-II (ATTGG-N-CCACG) as the second ER stress response element. Interestingly, ERSE-II was also dependent on p50ATF6, in a manner similar to that of ERSE, despite the disparate structure. The strong induction of Herp mRNA by ER stress would be achieved by the cooperation of ERSE and ERSE-II. (+info)
Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response. (7/241)The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCACG. We recently proposed that ER stress response factor (ERSF) binding to ERSE is a heterologous protein complex consisting of the constitutive component NF-Y (CBF) binding to CCAAT and an inducible component binding to CCACG and identified the basic leucine zipper-type transcription factors ATF6alpha and ATF6beta as inducible components of ERSF. ATF6alpha and ATF6beta produced by ER stress-induced proteolysis bind to CCACG only when CCAAT is bound to NF-Y, a heterotrimer consisting of NF-YA, NF-YB, and NF-YC. Interestingly, the NF-Y and ATF6 binding sites must be separated by a spacer of 9 bp. We describe here the basis for this strict requirement by demonstrating that both ATF6alpha and ATF6beta physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6alpha and ATF6beta bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6alpha and/or beta and capable of binding to ERSE is indeed formed when the cellular UPR is activated. We concluded that ATF6 homo- or heterodimers recognize and bind directly to both the DNA and adjacent protein NF-Y and that this complex formation process is essential for transcriptional induction of ER chaperones. (+info)
ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. (8/241)ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response. When unfolded proteins accumulate in the ER, ATF6 is cleaved to release its cytoplasmic domain, which enters the nucleus. Here, we show that ATF6 is processed by Site-1 protease (S1P) and Site-2 protease (S2P), the enzymes that process SREBPs in response to cholesterol deprivation. ATF6 processing was blocked completely in cells lacking S2P and partially in cells lacking S1P. ATF6 processing required the RxxL and asparagine/proline motifs, known requirements for S1P and S2P processing, respectively. Cells lacking S2P failed to induce GRP78, an ATF6 target, in response to ER stress. ATF6 processing did not require SCAP, which is essential for SREBP processing. We conclude that S1P and S2P are required for the ER stress response as well as for lipid synthesis. (+info)
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Methods: Using HepG2 cells, we inhibited UPR signaling using tunicamycin (Tu, 6uM) either with 450 uM leucine (L450) or without leucine (L0). To identify the UPR arms involved, cells were treated (24 hrs) with Tu in L450/L0 in presence or absence of Inositol-requiring enzyme 1( IRE-1) pathway inhibitor 4u8c (50uM), or PKR-like ER kinase (PERK )inhibitor GSK2656157 (1uM). Further, using Tu we activated UPR signaling in combination with/without mTOR activator MHY1485 (1uM) in L450 and L0. The subsequent effects on UPR activity were confirmed using Western blot. IGFBP-1 phosphorylation was assessed in cell media using phospho-site (pS101/ 119/169) specific IGFBP-1 antibodies ...
One family of proteins that senses conditions in the ER and increases the organelles folding capacity is comprised of a family of membrane-bound transcription factors, named after the founding member ATF6. We are interested in the molecular mechanisms behind the activity of ATF6 family proteins, as well as their functional roles in the cell. Read more…. ...
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Looking for online definition of Inositol-requiring protein 2 in the Medical Dictionary? Inositol-requiring protein 2 explanation free. What is Inositol-requiring protein 2? Meaning of Inositol-requiring protein 2 medical term. What does Inositol-requiring protein 2 mean?
In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase ...
Grp78/BiP is a 78kDa protein located within the lumen of the endoplasmic reticulum (ER), where it helps store Ca2+ and acts particularly as a chaperone assisting in the folding and assembly of membrane-bound or secretory proteins. Recent evidence has implicated the protein as a sensor of ER malfunction, regulating the initiation of a signalling pathway, known as the ER stress response or Unfolded Protein Response (UPR). The work undertaken for this thesis has addressed the role of Grp78/BiP in the mammalian UPR signalling pathway and the consequent effects upon cell survival, programmed cell death, and cell cycle regulation during ER stress. Novel Grp78/BiP fluorescent and bioluminescent chimeric proteins were generated in order to study dynamic changes of EGFP-tagged Grp78/BiP proteins located in the cell. This approach simplified and facilitated the generation of stable cell lines over-expressing Grp78/BiP and provided a powerful tool for single cell analysis to help determine its role in ...
Mitochondrial dysfunction is pervasive in human pathologies such as neurodegeneration, diabetes, cancer, and pathogen infections as well as during normal aging. Cells sense and respond to mitochondrial dysfunction by activating a protective transcriptional program known as the mitochondrial unfolded …
Specifically, our results confirmed direct targeting of miR-204 to the 3′UTRs of AP1S2, Bcl2l2, BIRC2, EDEM1, EZR, FZD1, M6PR, RAB22A, RAB40B, SERP1, TCF12, and TCF4 and demonstrated a significant decrease in the expression of Bcl2l2/Bcl-w, cIAP1/BIRC2, SERP1/RAMP4, M6PR, and EZR proteins induced by miR-204. Two of these genes, Bcl2l2/Bcl-w and cIAP1/BIRC2, are known to inhibit apoptosis. Bcl-w is a member of the Bcl-2 family, which inhibits apoptosis by interacting with proapoptotic members of the Bcl-2 family, such as Bad, Bax, and Bik, blocking the formation of the homodimers and, thus, the activation of the apoptotic cascade. 15,16 cIAP1/BIRC2 belongs to the family of antiapoptotic regulators known as inhibitors of apoptosis (IAP) proteins. Expression of cIAP1/BIRC2 is induced in conditions of ER stress through the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway and contributes to cellular adaptation to stress by inhibiting the ER stress-induced apoptotic program that is ...
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The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms. We found that MYC directly controls IRE1 transcription by binding to its promoter and enhancer. Furthermore, MYC forms a transcriptional complex with XBP1, a target of IRE1, and enhances its transcriptional activity. Importantly, we demonstrate that XBP1 is a synthetic lethal partner of MYC. Silencing of XBP1 selectively blocked the growth of MYC-hyperactivated cells. Pharmacological inhibition of IRE1 RNase activity with small molecule inhibitor 8866 selectively restrained the MYC-overexpressing tumor growth in vivo in a cohort of preclinical ...
Purpose: : Cataracts can be induced by the unfolded protein response (UPR), which initiates diversified pathways including the production of reactive oxygen species (ROS) and apoptosis. In the UPR pathway, cell death is induced by the activation of CHOP, a member of the C/EBP family of transcriptional factors, which suppresses the expression of Bcl2 and subsequently activates caspases. CHOP is activated by activating transcriptional factor 4 (ATF4) in the UPR. The UPR also activates the expression of the ledgf gene. Lens epithelium derived growth factor (LEDGF) previously has been defined as a survival factor and activates several antiapoptotic enzymes. The purpose of this study is to determine whether LEDGF is under the control of ATF4 and CHOP in the UPR pathway. Methods: : Human lens epithelial cells (LECs) were cultured with ER stressors such as 5mM homocysteine, 1uM calcium ionophore (A23187), or 5uM tunicamycin for 24 hrs. Total protein and RNA were extracted from the resultant cells. ...
The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes
Increasing evidence demonstrates that dysregulation of XBP1 function contributes to tumorigenesis in some cancers. However, little is known about the role of XBP1 in the progression of osteosarcoma (OS). The expression of XBP1 in OS samples was measured by quantitative RT-PCR and Western blotting assays. Cell cycle analysis and cell counting kit 8 (CCK8) assays were performed to determine the effects of XBP1 expression on cells growth capacity. Cell apoptosis coassay was applied to determine cell survival. The expression of genes affected by XBP1 was examined by quantitative RT-RCR and validated by Western blotting assays. XBP1 was overexpressed in OS clinical samples compared with corresponding non-cancerous tissues. Overexpression of XBP1 was significantly associated with advanced clinical stages, high degree of malignancy and low tumor necrosis rate. Furthermore, hypoxia activated XBP1, and silencing XBP1 significantly enhanced OS cell apoptosis. Knock-down of XBP1 resulted in inhibition of OS growth
The unfolded protein response (UPR) is a cellular stress response activated in eukaryotic cells in response to endoplasmic reticulum (ER) stress, an accumul...
Abstract The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) induces a coordinated adaptive program called the unfolded protein response (UPR). The..
Despite the relevance of the eukaryotic endoplasmic reticulum (ER)-stress response as an integrator of multiple stress signals into an adaptive response, knowledge about these ER-mediated cytoprotective pathways in soybean (Glycine max) is lacking. Here, we searched for genes involved in the highly conserved unfolded protein response (UPR) and ER stress-induced plant-specific cell death signaling pathways in the soybean genome. Previously characterized Arabidopsis UPR genes were used as prototypes for the identification of the soybean orthologs and the in silico assembly of the UPR in soybean, using eggNOG v4.0 software. Functional studies were also conducted by analyzing the transcriptional activity of soybean UPR transducers. As a result of this search, we have provided a complete profile of soybean UPR genes with significant predicted protein similarities to A. thaliana UPR-associated proteins. Both arms of the plant UPR were further examined functionally, and evidence is presented that the soybean
Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a type I endoplasmic reticulum transmembrane protein containing a stress-sensing domain facing the endoplasmic reticulum lumen and a cytosolic kinase domain. PERK is a major component of the unfolded protein response (UPR), which promotes the adaptation of cells to various forms of stress. PERK is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. PERK regulates proliferation of beta cells during embryonic and neonatal development and is essential for viability of acinar cells in mouse exocrine pancreas, neither of which is associated with endoplasmic reticulum stress response. PERK is also required for endoplasmic reticulum functions including proinsulin trafficking and quality control in beta cells. Similarly, PERK modulates proliferation and differentiation of osteoblasts as well as secretion of type I collagen. PERK phosphorylates α subunit of the translation ...
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In this study, we report that ER stress is induced by oxLDLs in human vascular cells and modulate the balance between survival and apoptosis induced by oxLDLs. The detection of ER stress markers (phospho-Ire1α and KDEL motif-bearing proteins) in human stable and advanced atherosclerotic lesions exhibiting high 4-HNE adduct staining indicates that lipid oxidation products (such as 4-HNE and 4-HNE-containing LDL) probably contribute to induce ER stress within the plaque. Forced expression of the ER-resident chaperone ORP150 inhibits ER stress induction triggered by oxLDLs by interacting with the ER stress sensors in vitro and in vivo in atherosclerotic lesions, which suggests that ORP150 could modulate ER stress in the vascular wall.. The first important result of this study is the induction of ER stress by oxLDLs and its potential involvement in oxLDL-induced apoptosis. The oxLDL-induced ER stress and UPR were assessed by the phosphorylation of ER stress sensors and the expression of ER-resident ...
The unfolded protein response (UPR) is an adaptive response that maintains the fidelity of the cellular proteome in conditions that subvert the folding capacity of the cell, such as those noticed in infection and inflammatory contexts. In immunity, the UPR sensor IRE1 (Inositol-requiring enzyme 1-al …
This study provides a novel perspective on the well-established link between UPR activation and FLD. Many studies have found some aspects of the UPR induced in FLD samples, and this has led to an oversimplification of the relationship between UPR activation and FLD, whereby any indicator of UPR activation is equated with ER stress and that all stressors that generate UPR induction cause FLD. Our data challenge this dogma by showing that (i) the UPR does not function as a rheostat in which all components behave synchronously in response to stress, but instead is characterized by distinct subclasses that change based on the nature and duration of the stress and (ii) some stressors induce a UPR subclass that causes FLD whereas other UPRs do not. Furthermore, our data confirm findings in other systems that an adaptive UPR can protect against the negative consequences of a robust stressor (Achard and Laybutt, 2012; Cinaroglu et al., 2011; Lugea et al., 2011; Rutkowski et al., 2006; Ye et al., 2010) ...
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The ability of cells and organisms to regulate protein homeostasis, or the balance of protein synthesis, assembly, folding, aggregation and secretion in the end...
@Valentijn @Violeta @Gondwanaland @ahmo @skwag @leela @jop @Tunguska I am tagging you all because this is very important. For the past two weeks i...
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GGCGTAATCT GCTGCTTGCA AACAAAAAAA CCACCGCTAC CAGCGGTGGT TTGTTTGCCG GATCAAGAGC TACCAACTCT TTTTCCGAAG GTAACTGGCT TCAGCAGAGC GCAGATACCA AATACTGTCC TTCTAGTGTA GCCGTAGTTA GGCCACCACT TCAAGAACTC TGTAGCACCG CCTACATACC TCGCTCTGCT AATCCTGTTA CCAGTGGCTG CTGCCAGTGG CGATAAGTCG TGTCTTACCG GGTTGGACTC AAGACGATAG TTACCGGATA AGGCGCAGCG GTCGGGCTGA ACGGGGGGTT CGTGCACACA GCCCAGCTTG GAGCGAACGA CCTACACCGA ACTGAGATAC CTACAGCGTG AGCATTGAGA AAGCGCCACG CTTCCCGAAG GGAGAAAGGC GGACAGGTAT CCGGTAAGCG GCAGGGTCGG AACAGGAGAG CGCACGAGGG AGCTTCCAGG GGGAAACGCC TGGTATCTTT ATAGTCCTGT CGGGTTTCGC CACCTCTGAC TTGAGCGTCG ATTTTTGTGA TGCTCGTCAG GGGGGCGGAG CCTATGGAAA AACGCCAGCA ACGCAAGCTA GCTTCTAGCT AGAAATTGTA AACGTTAATA TTTTGTTAAA ATTCGCGTTA AATTTTTGTT AAATCAGCTC ATTTTTTAAC CAATAGGCCG AAATCGGCAA AATCCCTTAT AAATCAAAAG AATAGCCCGA GATAGGGTTG AGTGTTGTTC CAGTTTGGAA CAAGAGTCCA CTATTAAAGA ACGTGGACTC CAACGTCAAA GGGCGAAAAA CCGTCTATCA GGGCGATGGC CGCCCACTAC GTGAACCATC ACCCAAATCA AGTTTTTTGG GGTCGAGGTG CCGTAAAGCA CTAAATCGGA ACCCTAAAGG GAGCCCCCGA ...
CCCATTCGCC ATTCAGGCTG CGCAACTGTT GGGAAGGGCG ATCGGTGCGG GCCTCTTCGC TATTACGCCA GCTGGCGAAA GGGGGATGTG CTGCAAGGCG ATTAAGTTGG GTAACGCCCA GGGTTTTCCC AGTCACGACG TTGTAAAACG ACGGCCAGTG CCAAGCTGAT CTAATCAATA TTGGCCATTA GCCATATTAT TCATTGGTTA TATAGCATAA ATCAATATTG GCTATTGGCC ATTGCATACG TTGTATCCAT ATCATAATAT GTACATTTAT ATTGGCTCAT GTCCAACATT ACCGCCATGT TGACATTGAT TATTGACTAG TTATTAATAG TAATCAATTA CGGGGTCATT AGTTCATAGC CCATATATGG AGTTCCGCGT TACATAACTT ACGGTAAATG GCCCGCCTGG CGACCGCCCA GCGACCCCCG CCCGTTGACG TCAATAGTGA CGTATGTTCC CATAGTAACG CCAATAGGGA CTTTCCATTG ACGTCAATGG GTGGAGTATT TACGGTAAAC TGCCCACTTG GCAGTACATC AAGTGTATCA TATGCCAAGT CCGCCCCCTA TTGACGTCAA TGACGGTAAA TGGCCCGCCT AGCATTATGC CCAGTACATG ACCTTACGGG AGTTTCCTAC TTGGCAGTAC ATCTACGTAT TAGTCATCGC TATTACCATG GTGATGCGGT TTTGGCAGTA CACCAATGGG CGTGGATAGC GGTTTGACTC ACGGGGATTT CCAAGTCTCC ACCCCATTGA CGTCAATGGG AGTTTGTTTT GGCACCAAAA TCAACGGGAC TTTCCAAAAT GTCGTAATAA CCCCGCCCCG TTGACGCAAA TGGGCGGTAG GCGTGTACGG TGGGAGGTCT ATATAAGCAG AGCTCGTTTA GTGAACCGTC ...
Roots are the frontier of plant body to perceive underground environmental change. ER stress response represents circumvention of cellular stress caused by various environmental changes; however, a limited number of studies are available on ER stress responses in roots. Here, we report the tunicamycin (TM) -induced ER stress response in Arabidopsis roots by monitoring expression patterns of BiP3, a representative marker for the response. Roots promptly responded to the TM-induced ER stress through induction of the similar sets of ER stress-responsive genes. However, not all cells responded uniformly to the TM-induced ER stress in roots, as BiP3 was highly expressed in root tips, an outer layer in elongation zone, and an inner layer in mature zone of roots. We suggest that ER stress response in roots has tissue specificity.
TY - JOUR. T1 - Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster. AU - Lindström, Riitta. AU - Lindholm, Päivi. AU - Kallijärvi, Jukka. AU - Palgi, Mari. AU - Saarma, Mart. AU - Heino, Tapio I.. PY - 2016/3/14. Y1 - 2016/3/14. KW - ENDOPLASMIC-RETICULUM STRESS. KW - NEUROTROPHIC FACTOR MANF. KW - DOPAMINERGIC-NEURONS. KW - GENE-EXPRESSION. KW - CDNF PROTECTS. KW - ERSE-II. KW - CELLS. KW - MODEL. KW - BRAIN. KW - YEAST. KW - 1184 Genetics, developmental biology, physiology. U2 - 10.1371/journal.pone.0151550. DO - 10.1371/journal.pone.0151550. M3 - Article. VL - 11. JO - PLoS One. JF - PLoS One. SN - 1932-6203. IS - 3. M1 - 0151550. ER - ...
Secreted and membrane proteins fold and mature in the lumen of the endoplasmic reticulum (ER) before they are delivered to other compartments in the endomembrane system, displayed on the cell surface, or released extracellularly. A collection of phylogenetically conserved signaling pathways, collectively termed the unfolded protein response (UPR), monitors conditions in the ER, sensing an insufficiency in the ERs protein-folding capacity (and hence the threat of misfolding) and communicates this information regarding the status of the ER lumen to gene expression programs of eukaryotic cells [reviewed in (1)]. UPR activation increases ER abundance to match needs by mediating expansion of the ER membrane (2) and populating the expanded organelle space with newly synthesized protein-folding machinery. This long-term, largely transcriptional control is accompanied by mechanisms that transiently decrease the flux of protein entering the ER. As such, the UPR is a paradigm for countless other feedback ...
IRE1 resides in the endoplasmic reticulum (ER) as a transmembrane protein with both serine-threonine kinase and endoribonuclease activities.
The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol. In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling.
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Cardiovascular disease constitutes a major and increasing health burden in developed countries. Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic
Being a major factory for protein synthesis, assembly, and export, the endoplasmic reticulum (ER) has a precise and robust ER quality control (ERQC) system monitoring its product line. However, when organisms are subjected to environmental stress, whether biotic or abiotic, the levels of misfolded proteins may overwhelm the ERQC system, tilting the balance between the capacity of and demand for ER quality control and resulting in a scenario termed ER stress. Intense or prolonged ER stress may cause damage to the ER as well as to other organelles, or even lead to cell death in extreme cases. To avoid such serious consequences, cells activate self-rescue programs to restore protein homeostasis in the ER, either through the enhancement of protein-folding and degradation competence or by alleviating the demands for such reactions. These are collectively called the unfolded protein response (UPR). Long investigated in mammalian cells and yeasts, the UPR is also of great interest to plant scientists. Among
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The unfolded protein response maintains protein homeostasis in the endoplasmic reticulum (ER), where the majority of transmembrane and secretory proteins are modified, folded and assembled. When the ER-resident folding machinery becomes overwhelmed, misfolded polypeptides accumulate and lead to ER stress, with toxic consequences to cells. To adjust the protein-folding capacity of the ER according to the needs of the cell, ER-resident sensor/transducer proteins constantly monitor the protein folding status in the ER lumen and take corrective actions to maintain proper ER function. This collection of conserved signaling pathways is termed the unfolded protein response (UPR).. Since its discovery some 20 years ago, our knowledge of the UPR has vastly expanded. Many of the initial insights were obtained from the budding yeast Saccharomyces cerevisiae, where a single signal transduction pathway is tasked with responding to ER stress. This pathway is initiated by the stress sensor/transducer IRE1, a ...
Involved in vesicular protein trafficking, mainly in the early secretory pathway. targeting. Involved in the maintenance of the Golgi apparatus. Appears to play a role in the biosynthesis of secreted cargo including processing. Involved in endoplasmic reticulum stress response. May play a role in the regulation of heat-shock response and apoptosis (By similarity).
Endoplasmic reticulum (ER) stress is an ancient conserved mechanism that allows cells, especially those with significant secretory function such as intestinal e...
The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling. van Vliet AR, Giordano F, Gerlo S, Segura I, Van Eygen S, Molenberghs G, Rocha S, Houcine A, Derua R, Verfaillie T, Vangindertael J, De Keersmaecker H, Waelkens E, Tavernier J, Hofkens J, Annaert W, Carmeliet P, Samali A, Mizuno H, Agostinis P. Mol Cell. 2017 Mar 2;65(5):885-899.e6. doi: 10.1016/j.molcel.2017.01.020. Epub 2017 Feb 23. ...
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Expression of the ATF in the ECV304 cells. Immunofluorescence was performed, and the resulting cells were observed under a laser scanning confocal microscope. (
According to the prediction of the involvement of bZIP transcription factors in the ER stress response, AtbZIP60 was identified by genome-wide screening based on genomic information on Arabidopsis. Tunicamycin and other reagents activating the ER stress response induced transcripts of AtbZIP60. From these results, we predicted that AtbZIP60 plays a role in the ER stress response. Because the expression profile of AtbZIP60 was close to that of BiP, induction of AtbZIP60 transcript was not considered to be the first trigger of activation for BiP expression. Instead, it was assumed that a conformational change of AtbZIP60 activates the expression of chaperone genes, such as BiP. This prediction was based on the fact that AtbZIP60 contains a putative TMD like that of ATF6 in mammalian cells. Specifically, it was hypothesized that AtbZIP60 is converted to a soluble form by ER stress and becomes localized to the nucleus, resulting in the activation of chaperone genes. Indeed, a truncated form of ...
ATF6, a membrane-anchored transcription factor from the endoplasmic reticulum (ER) that modulates the cellular response to stress as an effector of the unfolded-protein response (UPR), is a key player in the development of tumors of different origin. reticulum (ER) can be particularly affected by the presence of mutations in secretory proteins or by dynamic changes in the cellular microenvironment, events which are often encountered in cancers. In the ER, these events are sensed by specific sensors, which in turn trigger select Rabbit Polyclonal to CPB2 signaling pathways, collectively named the unfolded-protein response (UPR) (1). The UPR is an adaptive response that allows the cells to either overcome the stress or promote cell death in the case of overwhelming burden (1). Three ER-resident proteins, namely, the protein kinase PKR-like ER kinase (PERK), the inositol-requiring protein 1 alpha (IRE1), and the activating transcription factor 6 alpha (ATF6), have been identified as the major ...
Syk activates transcription factor NFκB. This transcription factor is responsible for the production of numerous inflammatory ... Ahrén IL, Eriksson E, Egesten A, Riesbeck K (2003). "Nontypeable Haemophilus influenzae activates human eosinophils through ... 6 (1): 33-43. doi:10.1038/nri1745. PMID 16341139. Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness ... It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, ...
It was later identified by the yeast-two hybrid system to bind to activating transcription factor 2 (ATF2) to repress ATF- ... "Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in ... JDP2 (gene) has been shown to interact with Activating transcription factor 2. GRCh38: Ensembl release 89: ENSG00000140044 - ... c-Jun dimerization protein 2 and activating transcription factor 3, recruit multiple HDAC members to the ATF3 promoter". ...
de 2001). «Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated ... de 1999). «Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors». Mol. Cell. Biol. (UNITED STATES) ... de 1999). «Regulation of the MEF2 family of transcription factors by p38». Mol. Cell. Biol. (UNITED STATES) 19 (1): 21-30. ISSN ... Entrez Gene: MAPK14 mitogen-activated protein kinase 14». *↑ Sayed, M; Kim S O, Salh B S, Issinger O G, Pelech S L (Jun. de ...
... activating transcription factor 1 (ATF1), serum response factor (SRF), and mRNA-binding protein tristetraprolin (TTP) In ... "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ... Yang SH, Galanis A, Sharrocks AD (Jun 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors ... Kyriakis JM, Avruch J (Apr 2001). "Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress ...
The experience of psychological stress activates transcription factors that activate genes. In a study by Cole et al., it was ... concluded that GABA-1 transcription factor activates the interleukin-6-gene. This gene codes for a protein that activates the ... Biochemistry, 77(6), 585-592. Duarte, A., Poderoso, C., Cooke, M., Soria, G., Cornejo Maciel, F., et al. (2012). Mitochondrial ...
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"A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB". Nature. 388 (6642): 548-54. doi: ... Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime ... Lee FS, Peters RT, Dang LC, Maniatis T (1998). "MEKK1 activates both IκB kinase α and IκB kinase β". Proc. Natl. Acad. Sci. U.S ... "Entrez Gene: NFKBIB nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta". Woronicz JD, Gao X, ...
Once activated, NF-κB transcription factors regulate genes that are implicated in many important cellular processes, including ... "A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB". Nature. 388 (6642): 548-54. doi: ... NF-κB transcription factors are normally held in an inactive state by the inhibitory proteins IκBs. IKK-α and IKK-β ... IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK ...
"A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB". Nature. 388 (6642): 548-54. doi: ... In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper ... is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. IκBα inhibits NF-κB by ... Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I ...
... and activating transcription factor 3". Cancer Prevention Research. 4 (1): 116-27. doi:10.1158/1940-6207.CAPR-10-0218. PMC ... transcription factor activity, sequence-specific DNA binding transcription factor recruiting. • GO:0001948 protein binding. • ... transcription, DNA-templated. • negative regulation of sequence-specific DNA binding transcription factor activity. • negative ... negative regulation of transcription, DNA-templated. • negative regulation of NF-kappaB transcription factor activity. • ...
"Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell. 96 (1): 143-52. doi: ... "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell. 96 (1): 143-52. doi: ... growth factors, oncogenes play a rule in tumorigenesis. Although the exact function of MEN1 is not known, the Knudson "two-hit ... 6 (13): 2285-90. doi:10.1093/hmg/6.13.2285. PMID 9361035. Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X ( ...
ETS1 activates MET transcription in vitro. MET transcription is activated by hypoxia-inducible factor 1 (HIF1), which is ... "Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway". ... Hypoxia also activates transcription factor AP-1, which is involved in MET transcription. MET pathway plays an important role ... MET activates the STAT3 transcription factor directly, through an SH2 domain. The beta-catenin pathway, a key component of the ...
Towatari M, Kanei Y, Saito H, Hamaguchi M (1998). "Hematopoietic transcription factor GATA-2 activates transcription from HIV-1 ... a transcription factor. The GATA family of transcription factors, which contain zinc fingers in their DNA binding domain, have ... Sp1 and GATA factors are necessary for basal transcription in endothelial cells". J. Biol. Chem. 270 (25): 15320-6. doi:10.1074 ... Zhang SB, He QY, Zhao H, Gui CY, Jiang C, Qian RL (2002). "Function of GATA transcription factors in hydroxyurea-induced HEL ...
Activating transcription factor ATF6 has been shown to interact with YY1 and Serum response factor. GRCh38: Ensembl release 89 ... ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ... biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors ... "Entrez Gene: ATF6 activating transcription factor 6". Li M, Baumeister P, Roy B, Phan T, Foti D, Luo S, Lee AS (2000). "ATF6 as ...
Another transcription factor NF-κB, which is also activated by UV light, also increases the expression of MMP-9. The up- ... UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation results in ... The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), ... vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of ...
Tang TT, Dowbenko D, Jackson A, Toney L, Lewin DA, Dent AL, Lasky LA (2002). "The forkhead transcription factor AFX activates ... FOXO transcription factors have been shown to be the down downstream effector molecules of insulin-like growth factor (IGF) ... Tang TT, Lasky LA (2003). "The forkhead transcription factor FOXO4 induces the down-regulation of hypoxia-inducible factor 1 ... transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1". J. Leukoc ...
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March 2001). "A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx ... 104 (6): 849-59. doi:10.1016/S0092-8674(01)00282-3. PMID 11290323. Cooper MS, Stewart PM (January 2005). "Diagnosis and ...
Ji L, Arcinas M, Boxer LM (1995). "The transcription factor, Nm23H2, binds to and activates the translocated c-myc allele in ... Postel EH, Berberich SJ, Flint SJ, Ferrone CA (1993). "Human c-myc transcription factor PuF identified as nm23-H2 nucleoside ... Co-transcription of this gene and the neighboring upstream gene (NME1) generates naturally occurring transcripts (NME1-NME2) ... 122 (6): 957-68. doi:10.1016/j.cell.2005.08.029. PMID 16169070. Negroni A, Venturelli D, Tanno B, Amendola R, Ransac S, Cesi V ...
... addition or removal of N-acetylglucosamine is a means of activating or deactivating enzymes or transcription factors. In ... InChI=1S/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8-/m1/s1 Y ... InChI=1/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8-/m1/s1 ... "Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease". Annual Review ...
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in ... TFAP2A transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)". Williams T, Tjian R (Apr 1991). " ... "RB and c-Myc activate expression of the E-cadherin gene in epithelial cells through interaction with transcription factor AP-2 ... a cell-type-specific transcription factor that activates inducible enhancer elements". Genes & Development. 2 (12A): 1557-69. ...
"Assignment of the human helix-loop-helix transcription factor gene musculin/activated B-cell factor-1 (MSC) to chromosome 8q21 ... a Novel Basic Helix-Loop-Helix Transcription Factor Expressed in Activated B Lymphocytes". Mol Cell Biol. 18 (6): 3130-9. PMC ... Knight JC, Keating BJ, Kwiatkowski DP (2004). "Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1". ... "Entrez Gene: MSC musculin (activated B-cell factor-1)". Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction ...
As a transcription factor, Pax6 activates and/or deactivates gene expression patterns to ensure for proper development of the ... transcription factor activity, sequence-specific DNA binding. • transcription factor binding. • protein kinase binding. • ... RNA polymerase II transcription factor activity, sequence-specific DNA binding. Cellular component. • cytoplasm. • cell nucleus ... This transcription factor is most noted for its use in the interspecifically induced expression of ectopic eyes and is of ...
... suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression". J. Immunol. 173 (6 ... Yao YL, Yang WM, Seto E (September 2001). "Regulation of transcription factor YY1 by acetylation and deacetylation". Mol. Cell ... "Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I". J. Biol. Chem. 278 (3): 1841-7. ... "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood. 98 (7): 2116-23. doi:10.1182/blood ...
This kinase is activated through its phosphorylation by MAP kinase kinases (MKKs), preferably by MKK6. Transcription factor ... suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression". J. Immunol. 173 (6 ... Deak M, Clifton AD, Lucocq LM, Alessi DR (1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated ... a major pneumococcal virulence factor, involves calcium influx and depends on activation of p38 mitogen-activated protein ...
Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1 and IRF4. ... First, the B cells have to encounter a foreign antigen, and are then required to be activated by T helper cells before they ... This is a type of safeguard to the system, almost like a two-factor authentication method. ... the activated B cell begins to differentiate into more specialized cells. Germinal center B cells may differentiate into memory ...
Myc Proto Oncogene Protein (Transcription Factor p64 or Class E... ... Transcription Factor p64 or Class E Basic Helix Loop Helix Protein 39 or MYC) - Pipeline Review, H2 2017 report by Global ... Myc protein is a transcription factor that activates expression of many genes through binding enhancer box sequences and ... Myc Proto Oncogene Protein (Transcription Factor p64 or Class E Basic Helix Loop Helix Protein 39 or MYC) - Myc (c-Myc) protein ...
Compare activating transcription factor 6 beta ELISA Kits from leading suppliers on Biocompare. View specifications, prices, ... activating transcription factor 6 beta ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody ... Your search returned 13 activating transcription factor 6 beta ELISA ELISA Kit across 3 suppliers. ... Bovine Cyclic AMP-dependent transcription factor ATF-6 beta (ATF6B) ELISA Kit ...
"Activating Transcription Factor 6" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ... This graph shows the total number of publications written about "Activating Transcription Factor 6" by people in Harvard ... Below are the most recent publications written about "Activating Transcription Factor 6" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Activating Transcription Factor 6". ...
... protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds ... gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein ... Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant ...
Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury.. [Kyung Hwan Jegal ... Activating transcription factor 6 (ATF6) bound to unfolded protein response elements of SESN2 promoter, transactivated SESN2, ...
Endoplasmic Reticulum Stress-Induced Formation of Transcription Factor Complex ERSF Including NF-Y (CBF) and Activating ... Endoplasmic Reticulum Stress-Induced Formation of Transcription Factor Complex ERSF Including NF-Y (CBF) and Activating ... Endoplasmic Reticulum Stress-Induced Formation of Transcription Factor Complex ERSF Including NF-Y (CBF) and Activating ... Endoplasmic Reticulum Stress-Induced Formation of Transcription Factor Complex ERSF Including NF-Y (CBF) and Activating ...
Cavy Activating Transcription Factor 6 ELISA Kit-AAB64434.1 (MBS013931) product datasheet at MyBioSource, ELISA Kits ... ATF6A: Transcription factor that acts during endoplasmic reticulum stress by activating unfolded protein response target genes ... This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic ... Kit for analyzing the presence of the Activating Transcription Factor 6 (ATF6) ELISA Kit target analytes in biological samples ...
A study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic ... activating_transcription_factor_6. A study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin- ... activating_transcription_factor_6.txt. · Last modified: 2018/07/25 11:27 by administrador. ... Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were applied to evaluate the expression of ...
Metal-activated transcription factor 1 (MTF1) mediates the induction of metallothioneins I and II by zinc and stress signals. ... Metal-activated transcription factor 1 (MTF1) mediates the induction of metallothioneins I and II by zinc and stress signals. ... Induction of metallothionein I by arsenic via metal-activated transcription factor 1. Critical role of c-terminal cysteine ... The findings demonstrate a critical role of the C-terminal cysteine cluster of MTF1 in arsenic sensing and gene transcription ...
High-yield expression in E. coli and refolding of the bZIP domain of activating transcription factor 5.. Ciaccio NA1, Moreno ML ... Activating transcription factor 5 (ATF5) recently has been demonstrated to play a critical role in promoting the survival of ... High-Yield Expression in E. coli and Refolding of the bZIP Domain of Activating Transcription Factor 5 ... High-Yield Expression in E. coli and Refolding of the bZIP Domain of Activating Transcription Factor 5 ...
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene. This gene ... Activating transcription factor 2 has been shown to interact with C-jun, Casein kinase 2, alpha 1, CREB binding protein, ... "Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in ... Activating transcription factor GRCh38: Ensembl release 89: ENSG00000115966 - Ensembl, May 2017 GRCm38: Ensembl release 89: ...
... and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse ... Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription ... Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription ... Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription ...
Activating Transcription Factor 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - ... Activating transcription factor 6 (ATF6) sequence polymorphisms in type 2 diabetes and pre-diabetic traits. (PMID: 17327457) ... ATF6 (Activating Transcription Factor 6) is a Protein Coding gene. Diseases associated with ATF6 include Achromatopsia 7 and ... Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 ...
activating transcription factor. eIF2α. eukaryotic initiation factor 2α. ER. endoplasmic reticulum. HA. hemagglutinin. ID. ... biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors ... Mitosin/CENP-F as a negative regulator of activating transcription factor-4. J. Biol. Chem. 280: 13973-13977. ... Activating transcription factor 4. Int. J. Biochem. Cell Biol. 40: 14-21. ...
... ... Depp increased the level of phosphorylated Erk and activated the Elk-1 transcription factor in human embryonal kidney 293 cells ... 2005 Jul;11(7):471-6. doi: 10.1093/molehr/gah186. Authors Hirohiko Watanabe 1 , Kohsuke Nonoguchi, Toshiharu Sakurai, Tomoko ...
Activating transcription factor 6 (ATF6) sequence polymorphisms in type 2 diabetes and pre-diabetic traits.. Chu WS1, Das SK, ... Activating transcription factor 6 (ATF6) is located within the region of linkage to type 2 diabetes on chromosome 1q21-q23 and ... Activating Transcription Factor 6 (ATF6) Sequence Polymorphisms in Type 2 Diabetes and Pre-Diabetic Traits ... Activating Transcription Factor 6 (ATF6) Sequence Polymorphisms in Type 2 Diabetes and Pre-Diabetic Traits ...
Activating Transcription Factor 6. ATF6 is a 670-aa ER transmembrane protein.33,34 In comparison to PERK and IRE-1, in the ... Okada T, Yoshida H, Akazawa R, Negishi M, Mori K. Distinct roles of activating transcription factor 6 (ATF6) and double- ... Thameem F, Farook VS, Bogardus C, Prochazka M. Association of amino acid variants in the activating transcription factor 6 gene ... and activating transcription factor (ATF)6, which serve as the proximal effectors of the endoplasmic reticulum stress response ...
Targeting the MEF2-Like Transcription Factor Smp1 by the Stress-Activated Hog1 Mitogen-Activated Protein Kinase. Eulàlia de ... Targeting the MEF2-Like Transcription Factor Smp1 by the Stress-Activated Hog1 Mitogen-Activated Protein Kinase ... Targeting the MEF2-Like Transcription Factor Smp1 by the Stress-Activated Hog1 Mitogen-Activated Protein Kinase ... Targeting the MEF2-Like Transcription Factor Smp1 by the Stress-Activated Hog1 Mitogen-Activated Protein Kinase ...
Class-I TCP Transcription Factors Activate the SAUR63 Gene Subfamily in Gibberellin-Dependent Stamen Filament Elongation. ... Class-I TCP Transcription Factors Activate the SAUR63 Gene Subfamily in Gibberellin-Dependent Stamen Filament Elongation ... Class-I TCP Transcription Factors Activate the SAUR63 Gene Subfamily in Gibberellin-Dependent Stamen Filament Elongation ... Class-I TCP Transcription Factors Activate the SAUR63 Gene Subfamily in Gibberellin-Dependent Stamen Filament Elongation ...
... but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a ... used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. ... Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate ... paradoxically increases translation of ATF4 mRNA to produce a transcription factor that activates expression of several UPR ...
Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre- ... Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ...
Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in ... Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in ... Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in ... Cinaroglu, A., Gao, C., Imrie, D., & Sadler, K. C. (2011). Activating transcription factor 6 plays protective and pathological ...
... spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation ... Activating Transcription Factor 6/genetics , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Cell Proliferation ... Activating Transcription Factor 6 Language: English Journal: Yonsei Medical Journal Year: 2013 Type: Article ... Leptin Protein Induces Proliferation of A549 Cells via Inhibition of PKR-Like ER Kinase and Activating Transcription Factor-6 ...
Activating Transcription Factor 4, Genetic Linkage, In Situ Hybridization, Mutation, Neoplasm Antigens, Neoplasm Proteins, ... CEP290 (also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP- ... The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4 ... The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. ...
Activating transcription factor-6. CHOP:. CCAAT/enhancer-binding Homologous protein. GADD:. Growth arrest and DNA damage ... The UPR includes at least three signaling pathways initiated by the kinases IRE1 and PERK and the transcription factor ATF6 [3 ... ROS could activate cell death processes directly by the oxidation of proteins, lipids, and/or nucleic acids or could act as ... and Ca2+ influx , several TRPC families have also been shown directly activated in response to oxidative stress . In ...
ATF6Mitogen-ActivaATF4ApoptosisKinaseATF2SubunitGENESPathwaysIRE1PERKInhibitionEukaryotic translation initiationMRNATumorInterleukinPhosphorylationProteinsUnfolded proteinATF5PromoterATF3InteractsNuclearCellularMediatesCREBELISA KitOverexpressionSecretionRegulatesTranscriptionalInduceGlucose1999CAMP responsStressAntigenKinasesContributesCytokinesExpressionActivatorPromotesMAPKReceptorModulatesSequenceActivationBZIP transcription factorMechanismExtracellularRegulator
- ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. (nih.gov)
- Activating transcription factor 6 (ATF6) bound to unfolded protein response elements of SESN2 promoter, transactivated SESN2, and increased SESN2 protein expression. (sigmaaldrich.com)
- We recently proposed that ER stress response factor (ERSF) binding to ERSE is a heterologous protein complex consisting of the constitutive component NF-Y (CBF) binding to CCAAT and an inducible component binding to CCACG and identified the basic leucine zipper-type transcription factors ATF6α and ATF6β as inducible components of ERSF. (asm.org)
- Furthermore, we showed that ERSF including NF-Y and ATF6α and/or β and capable of binding to ERSE is indeed formed when the cellular UPR is activated. (asm.org)
- MBS013931 is a ready-to-use microwell, strip plate Sandwich ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Activating Transcription Factor 6 (ATF6) ELISA Kit target analytes in biological samples. (mybiosource.com)
- A study first showed that inhibition of activating transcription factor 6 ( ATF6 ) by apelin -13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood brain barrier ( BBB ) disruption after SAH . (operativeneurosurgery.com)
- ATF6 (Activating Transcription Factor 6) is a Protein Coding gene. (genecards.org)
- Activating transcription factor 6 (ATF6) sequence polymorphisms in type 2 diabetes and pre-diabetic traits. (cdc.gov)
- Activating transcription factor 6 (ATF6) is located within the region of linkage to type 2 diabetes on chromosome 1q21-q23 and is a key activator of the endoplasmic reticulum stress response. (cdc.gov)
- This concerted and complex cellular response is mediated initially by three molecules, PKR-like ER kinase (PERK), activated transcription factor 6 (ATF6), and Inositol-requiring enzyme 1 (IRE1) [ 2 ]. (hindawi.com)
- The UPR is mediated by pathways initiated by PRKR-like endoplasmic reticulum kinase, inositol-requiring 1A/X box binding protein 1, and activating transcription factor 6 (ATF6), and each of these pathways has been implicated to have a protective or pathological role in FLD. (nyu.edu)
- Instead, depleting larvae of active Atf6 either through a membrane-bound transcription factor peptidase site 1 mutation or an atf6 morpholino injection protected them against steatosis caused by chronic ER stress, but exacerbated steatosis caused by acute TN treatment. (nyu.edu)
- Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2alpha, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR. (bvsalud.org)
- Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. (bvsalud.org)
- Together, these results suggest that derepression of ATF6-dependent transcription, through DREAM downregulation or pharmacological inhibition, may be neuroprotective in HD. (jci.org)
- DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). (jci.org)
- ATF6α transits to the Golgi compartment where it is cleaved by intramembrane proteolysis to generate a soluble active transcription factor. (nih.gov)
- ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecules. (genetex.com)
- This differential expression probably results from the activation of the ATF6 gene by Runx2 and its repression by the Sox6 transcription factor. (biologists.org)
- Three signaling pathways are involved in the UPR, and these are mediated by inositol-requiring enzyme-1 (IRE1, also known as ERN1), PKR-like ER resistant kinase (PERK, also known as EIF2AK3) and activation transcription factor 6 (ATF6), which act in concert to limit new protein synthesis and to increase the levels of chaperones. (biologists.org)
- In addition to induction of autophosphorylation and activation of IRE1 and PERK, ER stress also causes ATF6 transit through the Golgi complex, where it is activated through proteolytic cleavage by the enzymes S1P and S2P (also known as MBTPS1 and MBTPS2, respectively). (biologists.org)
- Furthermore, BMP2 is known to activate ER stress sensors, including ATF6 and OASIS (also known as CREB3L1). (biologists.org)
- Exposure of Saccharomyces cerevisiae to increases in extracellular osmolarity activates the stress-activated Hog1 mitogen-activated protein kinase (MAPK), which is essential for cell survival upon osmotic stress. (asm.org)
- Mitogen-activated protein kinase (MAPK) cascades are common signaling modules found in both higher and lower eukaryotic cells. (asm.org)
- Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils. (wikipathways.org)
- Involvement of p38 mitogen-activated protein kinase signaling pathway in the rapid induction of the 78-kDa glucose-regulated protein in 9L rat brain tumor cells. (wikipathways.org)
- Engagement of tumor necrosis factor (TNF) receptor 1 leads to ATF-2- and p38 mitogen-activated protein kinase-dependent TNF-alpha gene expression. (springer.com)
- These events are related to the p38 mitogen-activated protein kinase and activating transcription factor 2 pathway. (ahajournals.org)
- 15 This transcription factor is activated by phosphorylation of Ser133 residue, which is typically performed by protein kinase A. 16 However, other protein kinases such as extracellular signal-regulated kinases 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), calmodulin kinase (CaMK), and protein kinase B (PKB) have also been shown to phosphorylate and activate CREB. (ahajournals.org)
- Maternal hyperglycemia-induced oxidative stress triggers aberrant mitogen-activated protein kinase (MAPK) activity through an unknown mechanism, resulting in increased proapoptotic signaling ( 4 , 12 ). (sciencemag.org)
- Analysis of the role of the mitogen-activated protein kinase in mediating cyclic-adenosine 3′,5′-Monophosphate effects on prolactin promoter activity. (ohsu.edu)
- A role for the mitogen-activated protein kinase in mediating the ability of thyrotropin-releasing hormone to stimulate the prolactin promoter. (ohsu.edu)
- ATF4 belongs to the ATF/CREB family of basic region/leucine zipper transcription factors. (jimmunol.org)
- CEP290 (also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formation. (mdc-berlin.de)
- The transcription factor ATF4 (activating transcription factor 4) is induced by multiple PD-relevant stressors, such as endoplasmic reticulum stress and oxidative damage. (jneurosci.org)
- ATF4 levels are also upregulated in neuronal PC12 cells treated with the dopaminergic neuronal toxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). (jneurosci.org)
- In neuronal PC12 cells, silencing of ATF4 enhanced cell death in response to either 6-OHDA or MPP+. (jneurosci.org)
- ATF4 was also protective against 6-OHDA-induced death of cultured mouse ventral midbrain dopaminergic neurons. (jneurosci.org)
- One of the major effectors of the ERS response is ATF4 (activating transcription factor 4, or CREB2), a member of the ATF/CREB family of basic leucine zipper transcription factors. (jneurosci.org)
- PERK phosphorylates eukaryotic initiation factor 2 alpha (eIF2α) resulting in global mRNA translation attenuation, and concurrently selectively increases the translation of several mRNAs, including the transcription factor ATF4, and its downstream target CHOP. (nih.gov)
- Using DNA microarray and network analyses of macrophages, they show compelling evidence that ATF4, which is involved in the ER stress response, plays an essential role in IL-6 expression induced by various metabolic stresses, including ER stress. (diabetesjournals.org)
- Furthermore, they reveal that the ATF4 pathway has a synergistic effect on the Toll-like receptor-4 signaling pathway, enhancing IL-6 expression. (diabetesjournals.org)
- IL-6 has been shown to play crucial roles in insulin resistance and type 2 diabetes ( 19 ), raising the possibility that ATF4 signaling is a novel target for the treatment of metabolic diseases. (diabetesjournals.org)
- Recently, ALP upregulation was shown to coincide with endoplasmic reticulum (ER) stress-mediated vascular calcification, specifically with expression of the transcription factor ATF4. (biomedcentral.com)
- The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 ( Pdx1 ) regulates β-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 ( Atf4 ). (pnas.org)
- ESAT-6 inhibited T cell IFN-γ secretion through mechanisms that did not involve cellular cytotoxicity or apoptosis. (jimmunol.org)
- Faced with persistent ER stress, adaptation starts to fail and apoptosis occurs, possibly mediated through calcium perturbations, reactive oxygen species, and the proapoptotic transcription factor CHOP. (nih.gov)
- The induction of STAT1 gene by activating transcription factor 3 contributes to pancreatic beta-cell apoptosis and its dysfunction in streptozotocin-treated mice. (springer.com)
- Wei K, Liu L, Xie F, Hao X, Luo J, Min S. Nerve Growth Factor Protects the Ischemic Heart via Attenuation of the Endoplasmic Reticulum Stress Induced Apoptosis by Activation of Phosphatidylinositol 3-Kinase. (medsci.org)
- Endoplasmic reticulum (ER) stress, which is activated initially as a defensive response to eliminate the accumulated unfolded proteins, has shown a critical involvement in the ischemia induced myocardial apoptosis. (medsci.org)
- NGF was found to protect cardiomyocytes from hypoxia/reoxygenation or angiotensin induced apoptosis [ 6 ]. (medsci.org)
- Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. (wikipathways.org)
- Maternal diabetes is a substantial risk factor for neural tube defects, and available evidence suggests that the mechanism that links hyperglycemia to neural tube defects involves oxidative stress and apoptosis. (sciencemag.org)
- ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. (sciencemag.org)
- Maternal diabetes-induced NTDs are associated with increased oxidative stress and apoptosis ( 2 , 4 , 6 , 7 , 11 - 14 ) through an unknown mechanism. (sciencemag.org)
- IL-1β inhibits β-cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor nuclear factor (NF)-κB. (diabetesjournals.org)
- The secreted IFNs bind to receptors, activate the JAK-STAT pathway, and ultimately induce expression of hundreds of IFN-stimulated genes (ISGs), including dsRNA-dependent protein kinase (PKR), RNase L, a subset of TLRs (TLR3, TLR7) and RLRs (RIG-I), and IRF7 ( 16 ). (jimmunol.org)
- These transducers are inositol requiring (IRE) 1α, PKR-like ER kinase (PERK), and activating transcription factor (ATF) 6α. (nih.gov)
- IRE1α activation also recruits and activates the stress kinase JNK. (nih.gov)
- Increased expression of nerve growth factor (NGF) has been found in the myocardium suffered from ischemia and reperfusion (I/R). The pro-survival activity of NGF on ischemic heart has been supposed to be mediated by phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. (medsci.org)
- pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells. (wikipathways.org)
- Prolonged nuclear retention of activated extracellular signal-regulated kinase 1/2 is required for hepatocyte growth factor-induced cell motility. (wikipathways.org)
- Arachidonic acid activates mitogen-activated protein (MAP) kinase-activated protein kinase 2 and mediates adhesion of a human breast carcinoma cell line to collagen type IV through a p38 MAP kinase-dependent pathway. (wikipathways.org)
- 2015 ) protein kinase activates ATF2 (Bhoumik et al. (springer.com)
- Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene. (wikipedia.org)
- Los sustratos de esta quinasa incluyen diversas proteínas o factores de transcripción como ATF2 , MEF2C , MAX , el regulador del ciclo celular CDC25B y el supresor tumoral p53 , lo que sugiere un papel de esta quinasa en regulación del ciclo celular y la transcripción, así como en respuesta a estrés genotóxico. (wikipedia.org)
- Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins located on human chromosome 2q32 and was discovered by Maekawa et al. (springer.com)
- Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. (springer.com)
- Activating transcription factor 2 (ATF2) down-regulates hepatitis B virus X promoter activity by the competition for the activating protein 1 binding site and the formation of the ATF2-Jun heterodimer. (springer.com)
- ESAT-6 subunit vaccines induce protection against challenge with M. tuberculosis in mice ( 4 , 5 ), and a vaccine construct that includes ESAT-6 and Ag85 reduces the bacillary burden after challenge with M. tuberculosis in guinea pigs and nonhuman primates ( 6 , 7 ). (jimmunol.org)
- In a previous paper (Lehrbach and Ruvkun, 2016) we showed that the ER-associated SKN-1A/Nrf1 transcription factor activates proteasome subunit expression in response to proteasome dysfunction, but it was not established whether SKN-1A/Nrf1 adjusts proteasome capacity in response to other proteotoxic insults. (bioportfolio.com)
- cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. (semanticscholar.org)
- A pore loop residue controls subunit assembly in G protein-activated inwardly rectifying K+ channels. (mpg.de)
- It was found that the transcription factor Klf4 present at the promoter of an enzymatic subunit of telomerase ( TERT ), where it formed a complex with β-catenin . (wikipedia.org)
- It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the unfolded protein response. (harvard.edu)
- This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. (mybiosource.com)
- It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. (mybiosource.com)
- ATF6A: Transcription factor that acts during endoplasmic reticulum stress by activating unfolded protein response target genes. (mybiosource.com)
- Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. (genecards.org)
- Insulin is a polypeptide hormone formed by 51 amino acids [ 5 ] which once bound with its receptor, mainly expressed in the liver, muscular, and adipose tissue [ 6 ], and regulates a wide number of physiological processes that comprise gene mechanisms such as cellular growth and differentiation, expression of genes that code for enzymes that trigger glycogen, and lipid and protein synthesis. (hindawi.com)
- Yeast cells respond to osmotic stress by inducing the expression of a very large number of genes, and the Hog1 MAPK plays a critical role in gene transcription upon stress. (asm.org)
- Hot1, Msn2, and Msn4 activate transcription, whereas Sko1 represses and activates different subsets of osmotic-inducible and Hog1-regulated genes ( 15 , 17 , 18 ). (asm.org)
- Sko1 is an ATF/CREB factor that represses genes under nonstress conditions by the recruitment of the general corepressor complex Cyc8-Tup1. (asm.org)
- Global gene expression analyses carried out to dissect the specific roles for each transcription factor have revealed that each of these factors can account for a limited effect on global gene expression by regulation of a small subset of the osmostress-inducible genes ( 3 , 17 ). (asm.org)
- Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. (uniprot.org)
- In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes. (bionity.com)
- However activated GR can complex with these other transcription factors and prevent them from binding their target genes and hence repress the expression of genes that are normally upregulated by NF-κB or AP-1. (bionity.com)
- Gene regulatory proteins - transcription factors that will bind and activate genes. (brainscape.com)
- Vascular endothelial growth factor (VEGF), heme oxygenase 1 (HMOX1), basic helix-loop-helix domain containing, class B, 2 (BHLHB2), p21cip1 and DDIT4 - these transcripts were also upregulated - are known to be direct target genes [47,52, (nih.gov)
- High-throughput studies uncovered many new target genes of the Pax6 transcription factors during lens development. (wikipedia.org)
- Especially, for 4 publicly available gene expression datasets, the L 1/2 regularization method achieved its success using only about 2 to 14 predictors (genes), compared to about 6 to 38 genes for ordinary L 1 and elastic net regularization approaches. (biomedcentral.com)
- Signal transducer and activator of transcription 3 (Stat3) is a latent transcription factor that, upon activation, regulates transcription of downstream genes involved in cell proliferation, survival, cell migration, and tumorigenesis ( 4 - 7 ). (aacrjournals.org)
- Receptor-regulated protein kinases are an important signaling mechanism which permits events at the cell membrane to alter the transcription of specific genes. (ohsu.edu)
- The studies seek to identify the signal transduction pathways, specific DNA elements and transcription factors which are required for the tissue-specific, regulated expression of these pituitary hormone genes. (ohsu.edu)
- By assessing the magnitude of activation of UPR sensors and target genes in the liver of zebrafish larvae exposed to three commonly used ER stressors (tunicamycin, thapsigargin and Brefeldin A), we have identified distinct combinations of UPR sensors and targets (i.e. subclasses) activated by each stressor. (biologists.org)
- Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). (hindawi.com)
- Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. (bvsalud.org)
- Among them, the activation of self-reactive lymphocytes and their infiltration in the pancreas, followed by the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF- α ), which united with its membrane receptor on the PBC, activate intracellular signaling pathways that end in the induction of proapoptotic mechanisms and, in some cases, cell death through necroptosis [ 13 , 14 ]. (hindawi.com)
- We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70. (jimmunol.org)
- Leukemias expressing the constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD activate signaling pathways that increase genomic instability through generation of reactive oxygen species (ROS), DNA double-strand breaks (DSB), and error-prone repair. (aacrjournals.org)
- A thorough understanding of the molecular mechanism by which growth factors induce EMT may help in the development of agents that block EMT-inducing signals from the tumour microenvironment or to inhibit critical down- stream signal transduction pathways. (nature.com)
- RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. (kegg.jp)
- We confirmed that UPR and ERO pathways are activated in these models. (ufl.edu)
- Regulation of pol III transcription by nutrient and stress signaling pathways. (semanticscholar.org)
- Dimerization of core stress-sensing region (CSSR) of the ER luminal domain of IRE1 creates a shared central groove similar to the peptide binding domains of major histocompatibility complexes (MHCs) [ 6 - 8 ]. (hindawi.com)
- IRE1α autophosphorylation activates the RNase activity to splice XBP1 mRNA, to produce the active transcription factor sXBP1. (nih.gov)
- BMP2 is known to activate UPR signaling molecules, including PERK, C/EBP homologous protein (CHOP, also known as DDIT3) and IRE1α. (biologists.org)
- For example, the PKR phosphorylates eukaryotic initiation factor 2α (eIF2α), leading to global translation suppression and thus inhibition of viral replication ( 17 , 18 ). (jimmunol.org)
- Preincubation of ESAT-6 with CFP10 under conditions that favor dimer formation did not affect inhibition of IFN-γ. (jimmunol.org)
- Additionally, niclosamide reversed adipocyte-induced EMT with a correlated inhibition of IL-6/Stat3 activation and downregulation of EMT-TFs TWIST and SNAIL. (nature.com)
- Further, eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1), a component of the mammalian target of rapamycin (mTOR) pathway that inhibits protein translation through interaction with EIF4E, is regulated by ATF5 and likely is involved in apoptotic susceptibility through regulation of global translation. (pnas.org)
- A hypoxia response pathway via mTOR (mammalian target of rapamycin) including inactivation of EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) and finally resulting in increased mRNA translation is known to be inhibited by DDIT4 . (nih.gov)
- Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were applied to evaluate the expression of targets in both protein and mRNA levels. (operativeneurosurgery.com)
- Although phosphorylation of eIF2α results in global translational suppression, it specifically increases translation of activating transcription factor (ATF)4 through ribosomal leaky scanning of the mini open reading frames (ORFs) in the 5′-untranslated region (UTR) of the mRNA ( 19 , 22 , 23 ). (jimmunol.org)
- The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. (bvsalud.org)
- ESAT-6 decreased IFN-γ transcription and reduced expression of the transcription factors, ATF-2 and c-Jun, which normally bind to the IFN-γ proximal promoter and stimulate mRNA expression. (jimmunol.org)
- After treatment with 6-OHDA or MPP+, parkin protein levels fall, despite an increase in mRNA levels. (jneurosci.org)
- Functional expression and cellular mRNA localization of a G protein-activated K+ inward rectifier isolated from rat brain. (mpg.de)
- Long-term alcohol and high fat diet feeding resulted in higher levels of serum alanine aminotransferase, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) KO females than in either middle-aged (6 months) KOs or older (aged 16 months) wild type females. (frontiersin.org)
- Moreover, in wild-type bone marrow-transplanted chimeric P2Y 1 -deficient mice with an apolipoprotein E-deficient background, a strong reduction of adhesion molecule-dependent leukocyte recruitment was observed after local injection of tumor necrosis factor α and interleukin 1β, excluding a role for the platelet or other hematopoietic cell type P2Y 1 in these events. (ahajournals.org)
- Similarly, the in vitro adhesion of isolated mouse monocytes to tumor necrosis factor α-stimulated murine endothelial cell monolayers and their migration across the cell layers were strongly reduced in P2Y 1 -deficient compared with wild-type endothelial cells, as was the expression of the adhesion molecules P-selectin, Vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. (ahajournals.org)
- These adhesion molecules are upregulated by proinflammatory cytokines, such as tumor necrosis factor α (TNFα), the effects of which also include the induction of endothelial cell permeability, motility changes, and the secretion of additional cytokines. (ahajournals.org)
- Although NK cells are generally responsible for killing tumor cells, the rescued STAT5-deficient NK cells promote tumor formation by producing enhanced levels of the angiogenic factor VEGFA. (aacrjournals.org)
- Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133. (wikipathways.org)
- 15(S)-HETE induced expression and secretion of interleukin-6 (IL-6), as analyzed by RT-PCR and ELISA, respectively. (ahajournals.org)
- Recognition of viral pathogen-associated molecular patterns such as viral RNAs or DNAs by the pathogen recognition receptors triggers signaling cascades, ultimately leading to the activation of IRF3 and IRF7 that involves phosphorylation and nuclear accumulation of the two factors. (jimmunol.org)
- The regulation of C/EBPβ is exerted in many manners, phosphorylation , acetylation , activation and repression via others transcription factors, oncogenic elements or chemokines , autoregulation, etc. (bionity.com)
- Recently, it was shown that Stat3 is activated through novel and noncanonical mechanisms, including phosphorylation at S727. (aacrjournals.org)
- Our data suggest for the first time that S727 phosphorylation is sufficient to activate Stat3, thereby driving prostate tumorigenesis independent of Y705 phosphorylation. (aacrjournals.org)
- In addition to Y705 phosphorylation, phosphorylation of another conserved Stat3 residue, serine 727 (S727), has also been documented to activate Stat3 signaling. (aacrjournals.org)
- Recent studies show that Stat3 can be activated through S727 phosphorylation in the absence of Y705 phosphorylation in noncancerous cells ( 9 , 10 ). (aacrjournals.org)
- Thyrotropin-releasing hormone stimulates phosphorylation of the epidermal growth factor receptor in GH3 pituitary cells. (ohsu.edu)
- This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. (wikipedia.org)
- Activation of a MAPK results in modification of a set of target proteins, often transcription factors, that allow the generation of appropriate cellular responses to an external stimulus. (asm.org)
- The unfolded protein response (UPR) is activated upon the accumulation of misfolded proteins in the endoplasmic reticulum (ER) that are sensed by the binding immunoglobulin protein (BiP)/glucose-regulated protein 78 (GRP78). (nih.gov)
- Hai T, Hartman MG. The molecular biology and nomenclature of the ATF/CREB family of transcription factors: ATF proteins and homeostasis. (springer.com)
- Hai T, Liu F, Coukos WJ, Green MR. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. (springer.com)
- Transcription factors 1: bZIP proteins. (springer.com)
- CCAAT-enhancer-binding proteins (or C/EBPs) are a family of transcription factors that are composed of six members C/EBP α to C/EBP ζ. (bionity.com)
- Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. (genecards.org)
- If this balance is perturbed, ER stress ensues and an intracellular signal-transduction system, the ER stress response, also called the unfolded protein response, is activated. (ahajournals.org)
- During unfolded protein response an approximative 50 kDa fragment containing the cytoplasmic transcription factor domain is released by proteolysis. (abcam.com)
- Imbalances in osmolarity and inhibitors of ion channels cause osmotic stress, while protein synthesis inhibitors activate the unfolded protein response. (qiagen.com)
- Activating transcription factor 5 (ATF5) recently has been demonstrated to play a critical role in promoting the survival of human glioblastoma cells. (nih.gov)
- We identify a previously unknown function for activating transcription factor 5 (ATF5) in the apoptotic susceptibility of β cells. (pnas.org)
- Binds to promoter DNA and activates it. (brainscape.com)
- Serial 5′ deletions and site-directed mutagenesis of IL-6 promoter along with chromatin immunoprecipitation using anti-CREB antibodies showed that cAMP response element is essential for 15(S)-HETE-induced IL-6 expression. (ahajournals.org)
- Several recent studies have focused on the role of LIM homeodomain transcription factors and their co-activators in regulating pituitary hormone promoter activity. (ohsu.edu)
- The pituitary-specific transcription factor, Pit-1, can direct changes in the chromatin structure of the prolactin promoter. (ohsu.edu)
- The study analyzed human data and found that in those who had received chemotherapy, the gene Atf3 - a transcription factor activated by stress , implicated in the mechanism of cellular stress, and found in a variety of cancer cells - is overexpressed, compared with patients who were not administered chemotherapy. (medicalnewstoday.com)
- Kang Y, Chen CR, Massague J. A self-enabling TGFβ response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. (springer.com)
- Activating transcription factor 3 (ATF3) represses the expression of CCL4 in murine macrophages. (springer.com)
- We found that IFN regulatory factor (IRF)7, the master regulator of type I IFN gene expression, interacts with activating transcription factor (ATF)4, a key component of the integrated stress responses whose translation is induced by viral infection and various stresses. (jimmunol.org)
- Menin interacts with the AP 1 transcription factor JunD and represses lunD-activated transcription. (springer.com)
- The metabotropic GABAB receptor directly interacts with the activating transcription factor 4. (semanticscholar.org)
- Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. (ohsu.edu)
- Novel nuclear target for thrombin: activation of the Elk1 transcription factor leads to chemokine gene expression. (wikipathways.org)
- The glucocorticoid receptor ( GR ) also known as NR3C1 ( nuclear receptor subfamily 3, group C, member 1) is a ligand-activated transcription factor that binds with high affinity to cortisol and other glucocorticoids . (bionity.com)
-  It has two nuclear localization sequences that signals it to localize to the nucleus. (wikipedia.org)
- Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. (semanticscholar.org)
- 6-8 The ER stress response is designed to transmit information about the status of protein folding from the rough ER to other cellular locations. (ahajournals.org)
- Notably, activation of ER stress sensors is modulated by other cellular factors, in addition to the dissociation of GRP78. (hindawi.com)
- However, ESAT-6 also contributes to virulence in animal models, mediates cellular cytolysis, and inhibits IL-12 production by mononuclear phagocytes. (jimmunol.org)
- Sequestration of a transcription factor in a cellular membrane and releasing it on demand is an additional layer of gene regulation that is considered a rapid mode to reprogram a gene expression casca. (bioportfolio.com)
- Hai T. The ATF transcription factors in cellular adaptive responses. (springer.com)
- G protein-coupled receptors regulate gene expression by cellular signaling cascades that target transcription factors and their recognition by specific DNA sequences. (semanticscholar.org)
- Inwardly rectifying K+ (Kir) channels in Drosophila - A crucial role of cellular milieu factors for Kir channel function. (mpg.de)
- Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. (springer.com)
- Dominant-negative mutant-mediated blockade of ERK1/2, JNK1, p38MAPK, or CREB suppressed 15(S)-HETE-induced IL-6 expression in VSMCs. (ahajournals.org)
- Dominant-negative CREB also suppressed balloon injury-induced IL-6 expression, SMC migration from media to intimal region, and neointima formation. (ahajournals.org)
- Conclusions- The above results suggest a role for 15-LOX2-15-HETE in the regulation of VSMC migration and neointima formation involving CREB-mediated IL-6 expression. (ahajournals.org)
- cAMP-response element-binding protein (CREB) belongs to the basic leucine-zipper family of transcriptional factors that were shown to play an important role in gene regulation, particularly in response to cAMP. (ahajournals.org)
- 15,17 CREB forms homo- or heterodimers with members of either the CREB/activating transcriptional factor (ATF) or the activator protein-1 (AP-1) family of transcriptional factors. (ahajournals.org)
- ESAT-6 and CFP10 are secreted as a 1:1 dimer by a specialized ESAT-6 secretion system, ESX-1 ( 10 , 11 , 12 ). (jimmunol.org)
- ESAT-6 is produced in the lungs of mice infected with RD1-complemented M. bovis BCG ( 13 ), and gene deletion studies of M. tuberculosis , combined with reintroduction of RD1 into M. bovis BCG, demonstrated that secretion of ESAT-6 and CFP10 is required for virulence and pathogenicity of M. tuberculosis , both for growth in macrophages and in mice ( 13 , 14 , 15 ). (jimmunol.org)
- This study, for the first time, demonstrates that the TK target c-MYC plays a role in transcriptional activation and subsequent expression of LIG3 and PARP1 and contributes to the increased error-prone repair observed in TK-activated leukemias. (aacrjournals.org)
- What post-transcriptional factors affect gene expression? (brainscape.com)
- KLF4 can activate transcription by interacting via it N-terminus with specific transcriptional co-activators, such as p300-CBP coactivator family . (wikipedia.org)
- Transcription intermediary factor 1γ decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1. (ohsu.edu)
- All the members of the C/EBP family, except C/EBPγ, can induce transcription, through their activation domains, by interacting with components of the basal transcription apparatus. (bionity.com)
- Adipocytes induce epithelial mesenchymal transition of breast cancer cells through paracrine IL-6/Stat3 signalling. (nature.com)
- Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a tr. (nih.gov)
- Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV. (ohsu.edu)
- Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. (sigmaaldrich.com)
- ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK. (wikipedia.org)
- The steps involved in the prosurvival (blue steps 1 to 6) and proapoptotic phases (red steps 5′ to 8′) of the ER stress response are shown. (ahajournals.org)
- In general, during the prosurvival phase, components of the rapidly activated ER stress response contribute to restoring the ER luminal environment and resolving the ER stress, thus promoting survival. (ahajournals.org)
- However, if the ER stress is not resolved during the prosurvival phase, components of the ER stress response activated at later stages, during the proapoptotic phase, initiate the programmed cell death pathway. (ahajournals.org)
- There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. (hindawi.com)
- Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. (cdc.gov)
- Stress-activated protein kinases (SAPKs) are a subset of MAPKs activated by environmental and genotoxic stresses (reviewed in references 9 and 20 ). (asm.org)
- Msn2 and Msn4 are generic stress factors controlled by PKA and Hog1 by an unknown mechanism. (asm.org)
- a family of kinases activated in response to stress and inflammatory stimuli that modulates multiple aspects of cardiac fibroblast function, including inflammatory responses, myofibroblast differentiation, extracellular matrix turnover and the paracrine induction of cardiomyocyte hypertrophy. (mdpi.com)
- ER stress was a positive regulator of PRNP gene transcription in MCF-7 cells and luciferase reporter assays identified one ER stress response element (ERSE) conserved among primates and rodents and three primate-specific ERSEs that regulated PRNP gene expression. (biomedcentral.com)
- Constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD generate increased levels of reactive oxygen species (ROS), DNA damage including double-strand breaks (DSB), and abnormal repair that is highly error-prone. (aacrjournals.org)
- Both RXFP3 and RXFP4 inhibit cAMP production, and RXFP3 activate MAP kinases. (kegg.jp)
- In the context of TK-activated leukemias, c-MYC contributes to aberrant DNA repair through downstream targets LIG3 and PARP1, which represent viable and attractive therapeutic targets. (aacrjournals.org)
- Stat3 is aberrantly activated in various human cancers ( 6 ) and its signaling pathway contributes to the development of androgen-independent prostate cancer ( 4 ). (aacrjournals.org)
- This transcription factor is responsible for the production of numerous inflammatory cytokines and chemokines such as TNF, IL-23, IL-6, IL-2. (wikipedia.org)
- Activation of dectin-1 also triggers expression of many protecting antifungal cytokines and chemokines (TNF, CXCL2, IL-1b, IL-1a, CCL3, GM-CSF, G-CSF and IL-6) and the development of Th17. (wikipedia.org)
- High-yield expression in E. coli and refolding of the bZIP domain of activating transcription factor 5. (nih.gov)
- Depp increased the level of phosphorylated Erk and activated the Elk-1 transcription factor in human embryonal kidney 293 cells, suggesting that Depp modulates the effects of progesterone during decidualization and in the decidua by affecting gene expression. (nih.gov)
- ESAT-6, but not CFP10, bound to T cells and inhibited expression of early activation markers without reducing activation of ZAP70. (jimmunol.org)
- To understand how Hog1 controls gene expression, we designed a genetic screen to isolate new transcription factors under the control of the MAPK and identified the MEF2-like transcription factor, Smp1, as a target for Hog1. (asm.org)
- One mechanism by which SAPKs, and MAPKs in general, modulate gene expression is by direct modification of transcription activators. (asm.org)
- Thus, BCR-ABL1 or FLT3/ITD induces c-MYC expression, leading to genomic instability via augmented expression of ALT-NHEJ repair factors that generate repair errors. (aacrjournals.org)
- The role of cleaved activating transcription factor 6α (ΔATF6α) and spliced X-box protein-1 (sXBP1) in PRNP gene expression was assessed with over-expression or silencing techniques. (biomedcentral.com)
- As a transcription factor, Pax6 activates and/or deactivates gene expression patterns to ensure for proper development of the tissue. (wikipedia.org)
- This transcription factor is most noted for its use in the interspecifically induced expression of ectopic eyes and is of medical importance because heterozygous mutants produce a wide spectrum of ocular defects such as Aniridia in humans. (wikipedia.org)
- Adenovirus-mediated transduction of 15-lipoxygenase 2 (15-LOX2) caused increased production of 15-HETE in VSMCs and enhanced IL-6 expression, SMC migration from media to intimal region, and neointima formation in response to arterial injury. (ahajournals.org)
- Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1. (ohsu.edu)
- Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo-configuration that represses transcription to an active, expanded holo-form that promotes it. (diva-portal.org)
- Cardiac fibroblast-specific Activating Transcription Factors 3 promotes myocardial repair after myocardial infarction. (cmj.org)
- A direct mechanism of action involves homodimerization of the receptor, translocation via active transport into the nucleus , and binding to specific DNA responsive elements activating gene transcription . (bionity.com)
- It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. (wikipedia.org)
- GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and protein heterodimerization activity . (genecards.org)
- thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. (wikipedia.org)
- However, there is an alternative (ALT) version of NHEJ that results in larger deletions and chromosomal translocations where DNA ends are joined at regions of DNA sequence microhomology ( 6, 7 ). (aacrjournals.org)
- Could also be involved in activation of transcription by the serum response factor. (genecards.org)
- Deletion of the C-terminal cysteine cluster or mutation of the cysteine residues abolishes or markedly reduces the transcription activation activity of MTF1 and the ability of MTF1 to restore Mt1 induction in Mtf1 knockout cells. (cdc.gov)
- It is proposed that MHC-like groove binds portions of unfolded polypeptide chain to promote formation of higher-order oligomers necessary for UPR activation [ 6 - 8 ]. (hindawi.com)
- We evaluated the effects of ESAT-6 and its molecular chaperone, culture filtrate protein of 10 kDa (CFP10), on the capacity of human T cells to produce IFN-γ and proliferate in response to TCR activation. (jimmunol.org)
- Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. (uniprot.org)
- Background- Atherosclerosis is an inflammatory disease, and extracellular nucleotides are one of the factors possibly involved in vascular inflammation. (ahajournals.org)
- Among the various factors involved in all these processes, extracellular nucleotides and their receptors have been proposed to play a role. (ahajournals.org)