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 2.7.7.6.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 2.3.1.28.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 2.7.7.6.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)

*FOXO4

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 ...

*Proneural genes

Proneural bHLH transcription factors, not only drive neurogenesis by activating the expression of a cascade of neuronal genes, ... Proneural genes encode transcription factors of the basic helix-loop-helix (bHLH) class which are responsible for the ... The transcription factors responsible for this maintenance can act through the inhibition of the notch signaling pathway in ... Goulding, S. E.; White, N. M.; Jarman, A. P. (2000). "Cato encodes a basic helix-loop-helix transcription factor implicated in ...

*ATF6

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 ...

*CEP290

38 (6): 674-81. doi:10.1038/ng1786. PMID 16682973. Chang B, Khanna H, Hawes N, Jimeno D, He S, Lillo C, Parapuram SK, Cheng H, ... 6 (9): 791-806. doi:10.1101/gr.6.9.791. PMID 8889548. Nagase T, Ishikawa K, Nakajima D, et al. (1997). "Prediction of the ... 38 (6): 623-5. doi:10.1038/ng1805. PMID 16682970. den Hollander AI, Koenekoop RK, Yzer S, et al. (2006). "Mutations in the ... "The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4". Nat Genet. ...

*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: ...

*ATF1

1993). "Activating transcription factor-1 can mediate Ca(2+)- and cAMP-inducible transcriptional activation". J. Biol. Chem. ... Sun P, Lou L, Maurer RA (1996). "Regulation of activating transcription factor-1 and the cAMP response element-binding protein ... This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper ... Pongubala JM, Atchison ML (1995). "Activating transcription factor 1 and cyclic AMP response element modulator can modulate the ...

*Arsenic biochemistry

... which are induced by the activating transcription factor 6 (ATF6). If the number of erroneous proteins elevates, further ... Pi, J; Waalkes, MP; Kumagai, Y; Reece, JM; Qu, W (2003). "Transcription factor Nrf2 activation by inorganic arsenic in cultured ... Kumagai, Yoshito; Sumi, Daigo (2007). "Arsenic: Signal Transduction, Transcription Factor, and Biotransformation Involved in ... Kumagai, Yoshito; Sumi, Daigo Sumi (2007). "Arsenic: Signal Transduction, Transcription Factor, and Biotransformation Involved ...

*Protein disulfide-isomerase

... and activating transcription factor 6 (ATF6). They respond to high levels of misfolded proteins in the ER through intracellular ... 2010 (12): 6. doi:10.1038/nchembio.467. Kaplan A, Gaschler MM, Dunn DE, Colligan R, Brown LM, Palmer AG, Lo DC, Stockwell BR ( ... 17 (6): n/a-n/a. doi:10.1002/pmic.201600391. ISSN 1615-9861. PMC 5367942 . PMID 28044432. Soares Moretti, Ana Iochabel; Martins ... 6 (1): 6. doi:10.1186/1479-7364-6-6. PMC 3500226 . PMID 23245351. Perri, Emma R.; Thomas, Colleen J.; Parakh, Sonam; Spencer, ...

*EIF2AK3

Okada T, Yoshida H, Akazawa R, Negishi M, Mori K (2002). "Distinct roles of activating transcription factor 6 (ATF6) and double ... RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein ... Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum ... "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3". Søvik O, Njølstad PR, Jellum E, Molven A (May ...

*CREBL1

... and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response". Mol. Cell. Biol ... gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein ... gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein ... 2001). "Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) ...

*Unfolded protein response

... is upregulated downstream of the bZIP transcription factor ATF4 (activating transcription factor 4) and uniquely responsive to ... The activated domain is able to activate the transcription factor XBP1(Xbox binding protein) mRNA (the mammalian equivalent of ... The activated transcription factor upregulates UPR 'stress genes' by directly binding to stress element promoters in the ... ATF6 (activating transcription factor 6) is a basic leucine zipper transcription factor11.Upon Grp78 dissociation, the entire ...

*Adrenocortical hormone

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 ...

*HDAC3

... 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 ...

*MAPK11

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 ...

*CLEC7A

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, ...

*BCL-6 corepressor

"The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor". The Journal of ... The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription ... 36 (4): 411-6. doi:10.1038/ng1321. PMID 15004558. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA ... BCL-6 corepressor is a protein that in humans is encoded by the BCOR gene. ...

*Myocyte-specific enhancer factor 2A

Yang SH, Galanis A, Sharrocks AD (June 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors ... Myocyte-specific enhancer factor 2A is a protein that in humans is encoded by the MEF2A gene. MEF2A is a transcription factor ... Yang SH, Galanis A, Sharrocks AD (1999). "Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors". ... "Entrez Gene: MEF2A MADS box transcription enhancer factor 2, polypeptide A (myocyte enhancer factor 2A)". Mao Z, Nadal-Ginard B ...

*MAPK14

... 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 ...

*GATA2

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 ...

*Protein DEPP

... which is induced by progesterone in human endometrial stromal cells activates Elk-1 transcription factor". Mol. Hum. Reprod. 11 ... Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. GRCh38: Ensembl ... 7): 471-6. doi:10.1093/molehr/gah186. PMID 16123073. Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map ...

*Jun dimerization protein

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". ...

*Thymine-DNA glycosylase

G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription". J. Biol. Chem. ... 2002). "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell. 9 (2): ... 2003). "T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct ... "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell. 9 (2): 265-77. ...

*IL17A

... which in turn activates oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) and ... Other than the monoclonal antibodies, highly specific and potent inhibitors targeting Th17 specific transcription factor RORγt ... The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells. This cytokine regulates the ... Kolls JK, Khader SA (December 2010). "The role of Th17 cytokines in primary mucosal immunity". Cytokine & Growth Factor Reviews ...

*Adrenocorticotropic hormone deficiency

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 ...

*NFKBIB

"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, ...

*G1 phase

In order for the cell to continue through the G1-pm, there must be a high amount of growth factors and a steady rate of protein ... These complexes then activate S-Cdk complexes that move forward with DNA replication in the S phase. Concurrently, anaphase- ... the way this is phrased it is unclear whether it is transcription of the gene or translation of the mRNA gene product that is ... G1 phase and the other subphases of the cell cycle may be affected by limiting growth factors such as nutrient supply, ...

*MSC (gene)

"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 ...
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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?
BioAssay record AID 602332 submitted by NCGC: qHTS for Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in Human Glioma: qHTS.
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 ...
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. ...
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
Involvement of the unfolded protein response in lysosomal expansion and autophagy.Fat body cells mutant for Sec61α (A) or expressing RNAi against Sec61γ or Sr
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..
Studies have reported that development of congestive heart failure is associated with increased endoplasmic reticulum stress. Double stranded RNA-activated protein kinase R-like endoplasmic reticulum kinase (PERK) is a major transducer of the endoplasmic reticulum stress response and directly phosphorylates eukaryotic initiation factor 2α, resulting in translational attenuation. However, the physiological effect of PERK on congestive heart failure development is unknown. To study the effect of PERK on ventricular structure and function, we generated inducible cardiac-specific PERK knockout mice. Under unstressed conditions, cardiac PERK knockout had no effect on left ventricular mass, or its ratio to body weight, cardiomyocyte size, fibrosis, or left ventricular function. However, in response to chronic transverse aortic constriction, PERK knockout mice exhibited decreased ejection fraction, increased left ventricular fibrosis, enhanced cardiomyocyte apoptosis, and exacerbated lung remodeling ...
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Rapid and complex immune responses are induced in plants upon pathogen recognition. One form of plant defense response is a programmed burst in transcription and translation of pathogenesis-related proteins, of which many rely on ER processing. Interestingly, several ER stress marker genes are up-regulated during early stages of immune responses, suggesting that enhanced ER capacity is needed for immunity. Eukaryotic cells respond to ER stress through conserved signaling networks initiated by specific ER stress sensors tethered to the ER membrane. Depending on the nature of ER stress the cell prioritizes either survival or initiates programmed cell death (PCD). At present two plant ER stress sensors, bZIP28 and IRE1, have been described. Both sensor proteins are involved in ER stress-induced signaling, but only IRE1 has been additionally linked to immunity. A second branch of immune responses relies on PCD. In mammals, ER stress sensors are involved in activation of PCD, but it is unclear if plant ER
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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 ...
Membrane-associated and secreted proteins are synthesized and undergo early stages of processing--including folding into the proper conformation--within the endoplasmic reticulum (ER). Lipid components of the cells major membrane system are also synthesized in the ER, but how the amounts of ER proteins and lipids are coordinated is unclear. ER stress, which leads to an increased number of misfolded proteins, elicits the unfolded protein response (UPR). One element of the UPR involves activation of IRE1, an ER transmembrane kinase and endoribonuclease that cleaves the mRNA transcript for the transcription factor X-box binding protein 1 (XBP1) so that it encodes the active [XBP1(S)] rather than the inactive [XBP1(U)] form. XBP1(S) then stimulates the transcription of ER-resident proteins (see Ron and Hampton). Sriburi et al. transduced NIH-3T3 fibroblasts with retroviral vectors encoding XBP1(S) or XBP1(U) and found that cells overexpressing XBP1(S) showed increased ER volume and surface area, as ...
P.I. Merksamer, A.Trusina, F.R. Papa. Real-time redox measurements during endoplasmic reticulum stress reveal interlinked protein folding functions. Cell 135(5):933-47. Nov 28, 2008 ...
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The exciting paper by Ma et al. contributes to the accumulating evidence that PERK is involved in neurodegeneration and is potentially a therapeutic target (reviewed in (1)). Our group reported previously the activation of the unfolded protein response (UPR) in AD brain, including specific evidence for the activation of the translational PERK pathway. We detected the active form of the kinase and its phosphorylated substrate peIF2α (2,3)). This fits with the study by Ma et al. Essentially, these authors show that interference in basic homeostatic pathways can be employed to rescue deficits in synaptic plasticity in an APP/PS1 model. The authors are rightfully cautious to translate their findings to potential treatment for human disease, as interference in homeostatic stress pathways may also have a downside. It will be interesting to find out more mechanistic detail about the effects of PERK deletion on the progression of AD pathology, in particular tau pathology, as this is closely connected ...
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XBP1 antibody [N3C3] (X-box binding protein 1) for ICC/IF, IHC-P, WB. Anti-XBP1 pAb (GTX102229) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
The ability of cells and organisms to regulate protein homeostasis, or the balance of protein synthesis, assembly, folding, aggregation and secretion in the end...
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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 ...
CAAACAGGAT ATCTGTGGTA AGCAGTTCCT GCCCCGGCTC AGGGCCAAGA ACAGATGGAA CAGCTGAATA TGGGCCAAAC AGGATATCTG TGGTAAGCAG TTCCTGCCCC GGCTCAGGGC CAAGAACAGA TGGTCCCCAG ATGCGGTCCA GCCCTCAGCA GTTTCTAGAG AACCATCAGA TGTTTCCAGG GTGCCCCAAG GACCTGAAAT GACCCTGTGC CTTATTTGAA CTAACCAATC AGTTCGCTTC TCGCTTCTGT TCGCGCGCTT CTGCTCCCCG AGCTCAATAA AAGAGCCCAC AACCCCTCAC TCGGGGCGCC AGTCCTCCGA TTGACTGAGT CGCCCGGGTA CCCGTGTATC CAATAAACCC TCTTGCAGTT GCATCCGACT TGTGGTCTCG CTGTTCCTTG GGAGGGTCTC CTCTGAGTGA TTGACTACCC GTCAGCGGGG GTCTTTCATT TGGGGGCTCG TCCGGGATCG GGAGACCCCT GCCCAGGGAC CACCGACCCA CCACCGGGAG GCAAGCTGGC CAGCAACTTA TCTGTGTCTG TCCGATTGTC TAGTGTCTAT GACTGATTTT ATGCGCCTGC GTCGGTACTA GTTAGCTAAC TAGCTCTGTA TCTGGCGGAC CCGTGGTGGA ACTGACGAGT TCTGAACACC CGGCCGCAAC CCTGGGAGAC GTCCCAGGGA CTTTGGGGGC CGTTTTTGTG GCCCGACCTG AGGAAGGGAG TCGATGTGGA ATCCGACCCC GTCAGGATAT GTGGTTCTGG TAGGAGACGA GAACCTAAAA CAGTTCCCGC CTCCGTCTGA ATTTTTGCTT TCGGTTTGGA ACCGAAGCCG CGCGTCTTGT CTGCTGCAGC GCTGCAGCAT CGTTCTGTGT TGTCTCTGTC TGACTGTGTT TCTGTATTTG ...
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.
PERK is a transmembrane protein with an ER luminal stress-sensing domain that binds BiP and a cytosolic kinase domain (6). When ER stress is sensed, PERK multimerizes and phosphorylates eukaryotic translation initiation factor-α (eIF2α) (31). Phosphorylation of eIF2α inhibits general protein translation. However, a subset of genes that includes ATF4 (31) and nephrin (17) is preferentially translated by phosphorylated eIF2α. ATF4 in turn drives the transcription of specific UPR target genes, which include C/EBP homologous protein (CHOP, C/EBPζ, DDIT, GADD153) (24, 29, 57), GADD34 (58), TRB3 (73), osteocalcin, bone sialoprotein (90), receptor activator of NF-κB ligand (RANKL), E-selectin, VEGF (reviewed in Ref. 2), and genes important in amino acid metabolism (32). Recent work demonstrates that ATF4 augments expression of regulated in development and DNA damage responses 1 (Redd1) and Redd1 in turn inhibits mammalian target of rapamycin (mTOR) (40). Phosphorylated eIF2α (p- eIF2α) may also ...
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 - ...
IRE1 resides in the endoplasmic reticulum (ER) as a transmembrane protein with both serine-threonine kinase and endoribonuclease activities.
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ATF2兔多克隆抗体(ab28847)可与人样本反应并经WB, IP, ELISA, IHC实验严格验证,被5篇文献引用。所有产品均提供质保服务,中国75%以上现货。
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
Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function ...
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).
El factor de transcripción activador 6, también conocido como ATF6 (de sus siglas en inglés Activating Transcription Factor 6), es una proteína codificada en humanos por el gen atf6,[1]​[2]​[3]​ implicada en respuesta a la presencia de proteínas mal plegadas. ATF6 es un factor de transcripción transmembrana del retículo endoplasmático (RE) regulado por estrés que activa la transcripción de las moléculas del RE.[4]​ La acumulación de proteínas mal plegadas en el RE resulta en la proteolisis de ATF6. La región citosólica de ATF6 se translocará al núcleo y actuará como un factor de transcripción que activará la expresión de chaperonas del RE. [5]​== Interacciones == La proteína ATF6 ha demostrado ser capaz de interaccionar con: YY1[6]​ Factor de respuesta al suero[7]​ Factor de transcripción activador Hai TW, Liu F, Coukos WJ, Green MR (diciembre de 1989). «Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively ...
Endoplasmic reticulum (ER) stress is an ancient conserved mechanism that allows cells, especially those with significant secretory function such as intestinal e...
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Sigma-Aldrich offers abstracts and full-text articles by [Catrina Sims-Robinson, Anna Bakeman, Rebecca Glasser, Janet Boggs, Crystal Pacut, Eva L Feldman].
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Flies display metabolic changes during ER stress in vivo. (A) We fed male D. melanogaster w1118 with Tm (10 μg/mL, 23 hr) to induce ER stress and measured Ldh
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 ...
Tight repression of yeast endoplasmic reticulum stress sensor Ire1 by its N-terminal intrinsically disordered subdomainTight repression of yeast endoplasmic reticulum stress sensor Ire1 by its N-terminal intrinsically disordered subdomain ...
The unfolded protein response (UPR) allows cells to adjust secretory pathway capacity according to need. Ire1, the endoplasmic reticulum (ER) stress sensor and central activator of the UPR is conserved from the budding yeast Saccharomyces cerevisiae to humans. Under ER stress conditions, Ire1 clusters into foci that enable optimal UPR activation. To discover factors that affect Ire1 clustering, we performed a high-content screen using a whole-genome yeast mutant library expressing Ire1-mCherry. We imaged the strains following UPR induction and found 154 strains that displayed alterations in Ire1 clustering. The hits were enriched for iron and heme effectors and binding proteins. By pharmacological depletion and repletion, we confirmed that iron affects UPR activation in both yeast and human cells. We suggest that Ire1 clustering propensity depends on membrane composition, which is governed by heme-dependent biosynthesis of sterols. Our findings highlight the diverse cellular functions that feed ...
As the spread of sedentary lifestyle and obesity in the modern society, according to the data from World Health Organization (WHO), over 300 million people will suffer from diabetes mellitus by the year 2025 [32]. As one of the chronic cardiac complications, cardiovascular complications are major causes responsible for mortality of diabetes [33, 34]. In diabetes- afflicted population, increased risk for cardiac dysfunction which was termed as DCM which was considered independent from other cardiovascular diseases including hypertension, congenital heart disease, valvular heart diseases and coronary artery disease [35]. Apoptosis of cardiomyocytes is considered as one of the hallmarks of DCM, taking part in pathogenesis and progression of cardiac dysfunction during DCM [5, 36]. In this study, diabetes in rats was mimicked by intraperitoneal injection of STZ which selectively causes damage to islet beta cells to suppress insulin secretion. The induction of DCM was evidenced by cardiac pump and ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
The adaptive response of cells to increased unfolded proteins within the endoplasmic reticulum, or the unfolded protein response (UPR), is a fundamental and conserved cellular survival mechanism. Cancer development is often associated with a range of cytotoxic conditions like hypoxia, nutrient deprivation, and pH changes. These conditions trigger a set of cellular stress response pathways including the ER-stress response. Many aspects of the endoplasmic reticulum (ER)-stress response are adaptive and protect tumor cells from cell death suggesting a crucial role in tumor growth. Much less is known about the role of ER-stress response pathways in early stages of cancer and tumor progression. IRE1α is a major transducer of the UPR and is an ER localized transmembrane protein kinase/RNase. When activated by ER stress IRE1α splices an internal sequence from the XBP1 mRNA to generate a new transcript encoding the active XBP1 transcription factor, a major regulator of the adaptive response to ER ...
Endoplasmic reticulum stress with low-dose cyclosporine in frequently relapsing nephrotic syndrome.: An unfolded protein response due to ER stress induced by Cs
Activated Protein C Induces Endoplasmic Reticulum Stress and Attenuates Lipopolysaccharide-Induced Apoptosis Mediated by Glycogen Synthase Kinase-3β. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The Unfolded Protein Response (UPR) is a conserved and essential stress response that cells activate to combat endoplasmic reticulum (ER) stress, commonly caused by the accumulation of misfolded proteins or failing protein quality control. UPR signaling has been identified as one of the avenues leading to the inflammatory response. The integration of ER stress, oxidative stress and the inflammatory response is critical to the pathogenesis of a variety of diseases, such as diabetes, Alzheimers, Parkinsons, and obesity. It has been demonstrated that some cytokines can activate ER Stress and that ER stress can increase the expression of certain cytokines as well. Therefore, cytokine profiling provides a valuable tool for examining the relationship between cytokine expression and ER stress response. Signosis ER stress ELISA Strip allows quantitative profiling and measures 8 ER stress-associated cytokines. The list of cytokines is as follows: TNFα, IL-1β,IFNγ, IL-6 ,IGF-1, MCP-1, Leptin and ...
In cell systems, saturated fatty acids, compared to unsaturated fatty acids, induce a greater degree of ER stress and inflammatory signaling in a number of cell types, including hepatocytes and adipocytes. The aim of the present study was to determin
Diabetes may be a consequence of pancreatic cancer, preceding cancer diagnosis. The underlying mechanism is the release exosomes delivering adrenomedullin to β-cells, inducing endoplasmic reticulum stress and perturbations in the unfolded protein response, leading to β-cell dysfunction and death. This knowledge could lead to improved diagnostic strategies for pancreatic cancer. ...
Endoplasmic reticulum (ER) stress is caused by the accumulation of mis/unfolded proteins in the ER. ER stress signalling pathways termed the unfolded protein response are employed to alleviate ER stress through increasing the folding capacity and decreasing the folding demand of the ER as well as removing mis/unfolded proteins. However, ER stress signalling pathways induce diverse cellular changes beyond changes to the ER. This study aims to further investigate some of these ER stress-mediated events. ER stress can cause activation of JNK. Prolonged ER stress-mediated JNK activation is reported to promote apoptosis whilst both acute and long-lasting JNK activation is proposed to cause insulin resistance. To begin with it is reported in this thesis that acute ER stress-induced JNK activation, which is dependent on IRE1α and TRAF2, promotes survival. In contrast to other studies, this thesis provides evidence that acute ER stress-mediated JNK activation does not inhibit insulin signalling during ...
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimers disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the ...
Search PubMed for more publications by Feyza Engin. 1. Engin, F. "ER Stress and Development of Type 1 Diabetes" J Investig Med. 2015.. 2. Brozzi, F., Nardelli, TR., Lopes, M., Millard, I., Barthson, J., Igoillo-Esteve, M., Grieco, FA., Villate, O., Oliveira, JM., Casimir, M., Bugliani, M., Engin, F., Hotamisligil, GS., Marchetti, PM., Eizirik, DL. "Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms". Diabetologia. 2015.. 3. Engin, F., Ngyuen T., Yermalovich A., Hotamisligil, GS. "Aberrant unfolded protein response in type 2 diabetes". Sci Rep. 2014.. 4. Engin, F., Yermalovich, A., Fu, W., Ngyuen, T., Hummasti, S., Decio, L., Eizirik., Mathis, D., Hotamisligil, GS. "Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes". Sci. Transl. Med. 2013.. 5. Engin, F., Hotamisligil, GS. "Chemical modulation of ER function in metabolic diseases". Diabetes Obes. Metab. 2010. 12 Suppl 2:108-15.. 6. ...
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Despite improvement in recent surgery, radiation, and chemotherapy, the prognosis for patients with malignant glioma has not improved. Therefore, its even more urgent to search for new chemotherapeutic drugs. The aim of this project is to investigate the mechanism of perillyl alcohol (POH), an old chemotherapeutic agent, which has been recently used as intra-nasal inhalation in malignant glioma treatment. In this thesis, I document that POH alone, and combined with Dimethyl-celecoxib (DMC), shows significant anti-tumor activity in-vitro and triggers the induction of Glucose Related Protein 78 (GRP78), an anti-apoptotic protein that is elevated to deal with stress response. In addition, I also show induction of CCAAT/enhancer binding protein, or (CHOP), a pro-apoptotic protein signal for apoptosis, under the same treatments. These findings imply that POH alone generates Endoplasmic reticulum (ER) stress and forces the tumor cells to enter apoptosis, and when combined with DMC the effect is ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
The endoplasmic reticulum (ER) is an essential cellular compartment for protein synthesis and maturation and also functions as a Ca2+ storage organelle. The failure of the ER to cope with the excessive protein load due to perturbation of ER functions leads to ER stress. In response to ER stress, the unfolded protein response (UPR) is activated to reduce the unfolded protein load and meanwhile increase protein folding capacity. Activation of PERK (PKR-like eIF2a kinase) signaling and induction of ER chaperone GRP78/BiP (78kDa glucose-regulated protein) represent two major survival arms of the UPR. In this thesis, the fortuitous discovery of a novel cytosolic isoform of GRP78 is reported. This GRP78 isoform, designated as GRP78va, is generated by alternative splicing and alternative translational initiation. Expression of GRP78va is enhanced by ER stress and is notably elevated in human leukemic cells and leukemia patients. Unlike the canonical form of GRP78 which is primarily localized in the ER ...
Accumulation of malfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) and the upregulation of the ER molecular chaperones GRP78 and GRP 94 (1,2). These proteins are normally bound to ER transmembrane proteins such as IRE1p and ATF6 (3,4) but ER stress causes their dissociation. This allows IRE1p, a serine-threonine protein kinase to transduce the unfolded protein signal from the ER to the nucleus. IRE1p also has an endoribonuclease activity that is required to splice X-box binding protein (XBP1) mRNA converting it to a potent UPR transcriptional activation (5). Depletion of IRE1p through the expression of a dominant negative form of IRE1p has no effect on transfected cells, but cell death via apoptosis occurs under stress conditions that cause unfolded proteins to accumulate in the ER (6). Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. ...
The tight and fine-tuning regulation of ER stress response is fundamental in cell fate decision since UPR process is an evolutionarily conserved pathway for organism survival. Here, our findings show that ER stress promotes PHLDA3 gene induction in hepatocytes, facilitating cell death during the course of liver diseases. An important finding of this study is the discovery of PHLDA3 as a molecule that triggers hepatocyte injury elicited by ER stress. This outcome was supported by the analyses of clinical GEO databases; PHLDA3 was overexpressed in the liver of patients with cirrhosis; there was a variation in PHLDA3 mRNA level in these patients, probably reflecting individual differences in the degree of hepatocyte death (Xbp1s mRNA was not statistically different in this database presumably because of wide variations and/or difference in the mRNA half-life). We could see the significantly greater induction of PHLDA3 in HBV-infected patients with massive necrosis than those with submassive ...
The unfolded protein response (UPR), which is activated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum, has been implicated in the normal physiology of immune defense and in several human diseases, including diabetes, cancer, neurodegenerative disease, and inflammatory disease. Here, we found that the nervous system controlled the activity of a noncanonical UPR pathway required for innate immunity in Caenorhabditis elegans. OCTR-1, a putative octopamine G protein-coupled catecholamine receptor, functioned in sensory neurons designated ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes pqn/abu in nonneuronal tissues. Our findings suggest a molecular mechanism by which the nervous system may sense inflammatory responses and respond by controlling stress-response pathways at the organismal level.. ...
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM ...
It has been suggested that perturbation in the function of a subcellular organelle called the endoplasmic reticulum (ER) may determine the pathological effects of alpha-synuclein and other genetic forms of PD. In this target validation project we aimed to define the contribution of this stress pathway to PD using pre-clinical models of genetic and sporadic forms of the PD. By employing a gene therapy strategy to manipulate the levels of an essential factor of ER stress responses (termed XBP-1), we have defined possible therapeutic benefits of targeting the pathway in PD. We observed that the delivery of an active form of XBP-1 into the subtantia nigra of the model significantly protected neurons against the development of experimental PD. Moreover, using strategies that eliminate this factor in neurons we uncovered a fundamental role of XBP-1 in the normal function and survival of dopaminergic neurons. Our results indicate that the ER stress pathway is a potential therapeutic target to treat PD. ...
UNSPECIFIED (2002) ER quality control: A function for sugars in the cytosol. CURRENT BIOLOGY, 12 (19). R663-R665. ISSN 0960-9822 ...
Glucose-regulated protein 78 (GRP78) is expressed as part of the molecular response to endoplasmic reticulum (ER) stress and mediates protein folding within the cell. GRP78 is also an important...
Researchers in the lab of Gordon Weir, M.D., looked at a cellular stress mechanism called the unfolded protein response or endoplasmic reticulum (ER) stress response in beta cells. This response is triggered when the ER, part of the cells protein assembly line, struggles to fold newly formed proteins into their exactly right shapes.. Earlier studies suggested this process contributes to the high mortality and low insulin production often displayed in beta cell transplants, which aim to replace cells that the bodys own immune system kills off in type 1 diabetes.. In work reported in the journal PLoS One in June, the scientists compared healthy human beta cells from surgical donors with beta cells that had been transplanted into mice with suppressed immune systems. They found that the transplanted cells strongly activate genes that help to guard against damage from ER stress, and suppress other genes that may trigger cellular attempts to self-destruct.. "Not only is this response likely to be ...
The unfolded protein response (UPR) is an intracellular signaling pathway that is activated by the accumulation of unfolded proteins in the endoplasmic reticulum (ER). The UPR results in an increase in transcription of ER-resident proteins that facilitate protein folding in the ER. A key regulatory step in UPR activation is the regulated splicing of HAC1 mRNA, which encodes Hac1p, a transcription factor dedicated to this pathway. Hac1p can be detected only when the spliced form of HAC1 mRNA (termed HAC1i mRNA, for induced) is produced; this was surprising because the unspliced HAC1u mRNA (HAC1u for uninduced) is equally stable in cells.. ...
Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT)
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Myc Proto Oncogene Protein (Transcription Factor p64 or Class E Basic Helix Loop Helix Protein 39 or MYC) - Pipeline Review, H2...Myc Proto Oncogene Protein (Transcription Factor p64 or Class E Basic Helix Loop Helix Protein 39 or MYC) - Pipeline Review, H2...

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 ...
more infohttp://www.reportsnreports.com/reports/1222401-myc-proto-oncogene-protein-transcription-factor-p64-or-class-e-basic-helix-loop-helix-protein-39-or-myc-pipeline-review-h2-2017.html

Early Growth Response Protein 1
     Summary Report | CureHunterEarly Growth Response Protein 1 Summary Report | CureHunter

An early growth response transcription factor that has been implicated in regulation of CELL PROLIFERATION and APOPTOSIS. ... we showed here that E2F1 activated the expression of transcription factor EGR1 for promoting cell survival. ". 03/01/2002 - " ... EGR1 Transcription Factor; Early Growth Response Transcription Factor 1; Transcription Factor, EGR1 ... Transcription Factors: 20597*Early Growth Response Transcription Factors: 2*Early Growth Response Protein 1: 47*human EGR1 ...
more infohttp://www.curehunter.com/public/keywordSummaryD051766-Early-Growth-Response-Protein-1.do

activating transcription factor 6 beta ELISA Kits | Biocompare.comactivating transcription factor 6 beta ELISA Kits | Biocompare.com

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 ...
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Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. | Sigma-AldrichActivating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. | Sigma-Aldrich

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, ...
more infohttps://www.sigmaaldrich.com/catalog/papers/28433684

Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating...Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating...

... 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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/11256944

ATF6 elisa kit | Donkey Activating Transcription Factor 6 ELISA Kit-AAB64434.1ATF6 elisa kit | Donkey Activating Transcription Factor 6 ELISA Kit-AAB64434.1

Donkey Activating Transcription Factor 6 ELISA Kit-AAB64434.1 (MBS082135) 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 ...
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ATF6 elisa kit | Cavy Activating Transcription Factor 6 ELISA Kit-AAB64434.1ATF6 elisa kit | Cavy Activating Transcription Factor 6 ELISA Kit-AAB64434.1

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 ...
more infohttps://www.mybiosource.com/prods/ELISA-Kit/Cavy/Activating-Transcription-Factor-6/ATF6/datasheet.php?products_id=13931

activating transcription factor 6 [Operative Neurosurgery]activating transcription factor 6 [Operative Neurosurgery]

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 ...
more infohttps://operativeneurosurgery.com/doku.php?id=activating_transcription_factor_6

ATF6 Gene - GeneCards | ATF6A Protein | ATF6A AntibodyATF6 Gene - GeneCards | ATF6A Protein | ATF6A Antibody

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 ...
more infohttp://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=22926

Endoplasmic Reticulum Stress in the Heart | Circulation ResearchEndoplasmic Reticulum Stress in the Heart | Circulation Research

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 ...
more infohttp://circres.ahajournals.org/content/101/10/975

ER stress-induced cell death mechanisms.  - PubMed - NCBIER stress-induced cell death mechanisms. - PubMed - NCBI

... activating transcription factor 4; activating transcription factor 6; advanced glycated end-products; age-related macular ... Activated IRE1α can recruit TRAF2 and ASK1, which subsequently activates JNK. JNK-mediated phosphorylation of Bcl-2 releases ... Reduction in ATP levels (rise in AMP) activates the intracellular energy sensor AMPK, which activates autophagy via effects on ... transcriptional factor C/EBP homologous protein; type 2 diabetes; unfolded protein response; vascular endothelial growth factor ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/23850759?dopt=Abstract

Amelioration of Glucolipotoxicity-Induced Endoplasmic Reticulum Stress by a Chemical Chaperone in Human THP-1 MonocytesAmelioration of Glucolipotoxicity-Induced Endoplasmic Reticulum Stress by a "Chemical Chaperone" in Human THP-1 Monocytes

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 [30], several TRPC families have also been shown directly activated in response to oxidative stress [31]. In ...
more infohttps://www.hindawi.com/journals/jdr/2012/356487/

Endoplasmic reticulum stress-induced apoptosis in the development of diabetes: is there a role for adipose tissue and liver? |...Endoplasmic reticulum stress-induced apoptosis in the development of diabetes: is there a role for adipose tissue and liver? |...

1). ER stress sensors [IRE1 (inositol requiring 1), ATF6 (activated transcription factor 6) and PERK (ER-resident PKR-like eIF2 ... Role for activating transcription factor 3 in stress-induced β-cell apoptosis. Mol Cell Biol 24:5721-5732. doi: 10.1128/mcb. ... 3): (1) the proapoptotic pathway of CHOP/GADD153 transcription factor which is mainly induced via PERK/eIF2, (2) IRE1-mediated ... The cleaved N-terminal fragment migrates to the nucleus, acts as an active transcription factor, and increases the expression ...
more infohttps://link.springer.com/article/10.1007%2Fs10495-009-0400-4

Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes TherapyPancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy

a) Homeostasis: activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and PKR-like ER kinase (PERK) ... Three key UPR sensors mediate the correct functioning of the ER: activating transcription factor 6 (ATF6), inositol-requiring ... activating transcription factor 6; IRE1: inositol-requiring enzyme 1; eIF2α: eukaryotic initiation factor 2; mRNA: messenger ... inhibitor of nuclear factor kappa B kinase; IKB: NF-κB inhibitor; NF-κB: nuclear factor kappa B; PDX1: insulin promoter factor ...
more infohttps://www.hindawi.com/journals/jdr/2018/9601801/

Frontiers | Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER...Frontiers | Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER...

... the signal transducers and activators of transcription) in the older knockout female fed alcohol. Our results suggest that long ... Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2), Herpud1 (ubiquitin-like ... Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2), Herpud1 (ubiquitin-like ... the signal transducers and activators of transcription) in the older knockout female fed alcohol. Our results suggest that long ...
more infohttps://www.frontiersin.org/articles/10.3389/fgene.2013.00224/full

Endoplasmic reticulum-associated SKN-1A/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity.Endoplasmic reticulum-associated SKN-1A/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity.

Activating Transcription Factor 6. One of the BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS that is synthesized as a membrane- ... In a previous paper (Lehrbach and Ruvkun, 2016) we showed that the ER-associated SKN-1A/Nrf1 transcription factor activates ... It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the ...
more infohttps://www.bioportfolio.com/resources/pmarticle/2342471/Endoplasmic-reticulum-associated-SKN-1A-Nrf1-mediates-a-cytoplasmic-unfolded-protein-response.html

KEGG BRITE: KEGG Orthology (KO) - Tupaia chinensis (Chinese tree shrew)KEGG BRITE: KEGG Orthology (KO) - Tupaia chinensis (Chinese tree shrew)

102473406 ATF2; activating transcription factor 2 102478154 ATF4; activating transcription factor 4 102471928 CREB3L2; cAMP ... cyclic AMP-dependent transcription factor ATF-2 K04374 ATF4; cyclic AMP-dependent transcription factor ATF-4 K09048 CREB3; ... 102484080 ATF6B; activating transcription factor 6 beta 102475802 ATF1; activating transcription factor 1 102489009 DAGLB; ... activating transcription factor 1 K13806 DAGL; sn1-specific diacylglycerol lipase [EC:3.1.1.-] K13806 DAGL; sn1-specific ...
more infohttp://www.genome.jp/kegg-bin/get_htext?tup00001+102491327

GO Gene ListGO Gene List

Activating transcription factor 6. NM_007348. Gene Info. ATP6V0A1. ATPase, H+ transporting, lysosomal V0 subunit a1. NM_ ... Activating transcription factor 3. NM_001040619. NM_001674. NM_001206488. NM_001206484. NM_001206486. NM_001030287. Gene Info. ... Activating transcription factor 4 (tax-responsive enhancer element B67). NM_001675. NM_182810. Gene Info. ... ADP-ribosylation factor GTPase activating protein 1. NM_175609. NM_018209. Gene Info. ...
more infohttps://cgap.nci.nih.gov/Genes/GoGeneQuery?PAGE=1&ORG=Hs&GOID=0070887

Expression of ATF6 in cancer - Summary - The Human Protein AtlasExpression of ATF6 in cancer - Summary - The Human Protein Atlas

Activating transcription factor 6. Protein classi. Protein class the gene product belongs to according to selected gene lists. ... Activating transcription factor 6 (HGNC Symbol). Entrez gene summary. This gene encodes a transcription factor that activates ... GO:0003700 [transcription factor activity, sequence-specific DNA binding]. GO:0003713 [transcription coactivator activity]. GO: ... Transcription factors. Basic domains. Disease related genes. Protein evidence (Kim et al 2014). Protein evidence (Ezkurdia et ...
more infohttps://www.proteinatlas.org/ENSG00000118217-ATF6/pathology

ATF6 Antibody (70B1413.1) [PerCP] (NBP1-40256PCP): Novus BiologicalsATF6 Antibody (70B1413.1) [PerCP] (NBP1-40256PCP): Novus Biologicals

Activating transcription factor 6 alpha. *activating transcription factor 6. *atf6 a. *ATF6 alpha ... The protein ATF6 is a constitutively expressed transcription factor that is a key mediator of the unfolded protein response ( ... The ATF6 endoplasmic reticulum (ER) stress-regulated transcription factor is constitutively expressed and plays a central role ... Review with no image -- $10/€7/£6/$10 CAD/¥70 Yuan/¥1110 Yen ... cAMP-dependent transcription factor ATF-6 alpha. *cyclic AMP- ...
more infohttps://www.novusbio.com/products/atf6-antibody-70b14131_nbp1-40256pcp

KEGG PATHWAY: hsa04918KEGG PATHWAY: hsa04918

ATF2; activating transcription factor 2 [KO:K04450]. 468 ATF4; activating transcription factor 4 [KO:K04374]. ... PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]. ... PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]. ... PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]. ...
more infohttps://www.genome.jp/dbget-bin/www_bget?hsa04918

Endoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancer | Breast Cancer Research | Full TextEndoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancer | Breast Cancer Research | Full Text

ER stress was a positive regulator of PRNP gene transcription in MCF-7 cells and luciferase reporter assays identified one ER ... The role of cleaved activating transcription factor 6α (ΔATF6α) and spliced X-box protein-1 (sXBP1) in PRNP gene expression was ... The role of cleaved activating transcription factor 6α (ΔATF6α) and spliced X-box protein-1 (sXBP1) in PRNP gene expression was ... Regulation of prion gene expression by transcription factors SP1 and metal transcription factor-1. J Biol Chem. 2009, 284: 1291 ...
more infohttps://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr3398

Cholecystokinin | Article about cholecystokinin by The Free DictionaryCholecystokinin | Article about cholecystokinin by The Free Dictionary

Abbreviations: Ag: antigen; AMP: anti-microbial peptide; APC: Antigen presenting cell; ATF6: activating transcription factor 6 ...
more infohttps://encyclopedia2.thefreedictionary.com/cholecystokinin

JCI -
Volume 126, Issue 2JCI - Volume 126, Issue 2

... sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear ... These transcription factors include NF-κB and the HIV transactivator of transcription (Tat) as well as the cyclin-dependent ... The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its ... An analysis of monocyte nuclear lysates revealed that the transcription factor ICBP90 (also known as UHRF1) is the major ...
more infohttps://www.jci.org/126/2

anti-ATF6 antibody, Internal  | GeneTexanti-ATF6 antibody, Internal | GeneTex

... activating transcription factor 6) for FACS, IHC-P, WB. Anti-ATF6 pAb (GTX81096) is tested in Human samples. 100% Ab-Assurance. ... ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ... ATF6alpha, ATF6-alpha, ATF6, Processed cyclic AMPdependent transcription factor ATF6 alpha, Activating transcription factor6 ... Activating transcription factor 6 alpha, cAMPdependent transcription factor ATF6 alpha, ATF6 alpha. ...
more infohttp://www.genetex.com/ATF6-antibody-Internal-GTX81096.html
  • 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)
  • Your search returned 13 activating transcription factor 6 beta ELISA ELISA Kit across 3 suppliers. (biocompare.com)
  • 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)
  • 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)
  • While glucolipotoxicity/tunicamycin increased oxidative stress, ER stress, mRNA expression of TRPC-6, and programmed the THP-1 monocytes towards apoptosis, all these molecular perturbations were resisted by PBA. (hindawi.com)
  • Clinical and experimental evidence indicates that inflammatory processes in the vascular wall are the decisive factor that accounts for the rate of lesion formation and clinical development in patients suffering from atherosclerosis [ 2 ]. (hindawi.com)
  • 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)
  • Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. (sigmaaldrich.com)
  • 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)
  • 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)
  • Chronic ER stress is emerging as a trigger that imbalances a number of systemic and arterial-wall factors and promote atherosclerosis. (hindawi.com)
  • However, lack of hot-spot BRAF , RAS , or NF1 driver mutations in the triple wild-type subtype accounting for 6-20% of melanomas [ 2 , 3 ], and variability of phenotype of patient-derived melanoma cell lines representing the same genetic subtype [ 4 ] enforce combining both genetic and phenotypic traits to achieve more accurately stratification of melanoma patients. (springer.com)