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.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.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.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.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.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.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.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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.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.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.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.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.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.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.STAT6 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-4. Stat6 has been shown to partner with NF-KAPPA B and CCAAT-ENHANCER-BINDING PROTEINS to regulate GENETIC TRANSCRIPTION of interleukin-4 responsive 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.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.Basic Helix-Loop-Helix Transcription Factors: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.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)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).Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.PhosphoproteinsTyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.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).Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.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.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.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.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.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.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.STAT2 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to TYPE I INTERFERONS. Stat2 protein is associated constitutively with INTERFERON REGULATORY FACTOR-9. After PHOSPHORYLATION Stat2 forms the IFN-STIMULATED GENE FACTOR 3 COMPLEX to regulate expression of target GENES.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.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.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.STAT4 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-12 in T-LYMPHOCYTES. Stat4 is an important signaling molecule for differentiation in TH1 CELLS.STAT Transcription Factors: A family of transcription factors containing SH2 DOMAINS that are involved in CYTOKINE-mediated SIGNAL TRANSDUCTION. STAT transcription factors are recruited to the cytoplasmic region of CELL SURFACE RECEPTORS and are activated via PHOSPHORYLATION. Once activated they dimerize and translocate into the CELL NUCLEUS where they influence GENE expression. They play a role in regulating CELL GROWTH PROCESSES and CELL DIFFERENTIATION. STAT transcription factors are inhibited by SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS and PROTEIN INHIBITORS OF ACTIVATED STAT.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Phosphoserine: The phosphoric acid ester of serine.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.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.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.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.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.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.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.Activating Transcription Factor 3: An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds.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.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.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.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.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.Kinetics: The rate dynamics in chemical or physical systems.Mice, Inbred C57BLZinc 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.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.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.Transcription Initiation Site: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.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).)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.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.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.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.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.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.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.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.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.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.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.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.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.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.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.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.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.Milk Proteins: The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.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.GATA2 Transcription Factor: An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.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.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.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.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.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.Active Transport, Cell Nucleus: Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.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.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).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.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.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.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.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.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.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.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.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.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.PhosphopeptidesModels, 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.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.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.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.Nerve Tissue ProteinsCell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.GATA6 Transcription Factor: A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and regulates vascular smooth muscle CELL DIFFERENTIATION.Fungal Proteins: Proteins found in any species of fungus.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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.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.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.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.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.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)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.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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.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.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.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.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.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Bacterial Proteins: Proteins found in any species of bacterium.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.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.NIH 3T3 Cells: A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.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.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesSOX9 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.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)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.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.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).Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Leucine Zippers: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.Transcription 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.
ETS1The protein encoded by this gene belongs to the ETS family of transcription factors. There are 28 ETS genes in humans and 27 ... Such phosphorylation of ETS1 alters its target gene repertoire. The Ku80 portion of DNA-PK, acting alone, interacts with ETS1 ... Dwyer J, Li H, Xu D, Liu JP (Oct 2007). "Transcriptional regulation of telomerase activity: roles of the Ets transcription ... AP1, STAT5 and VDR bind to C-terminal domain. Also, ETS1 has been shown to interact with TTRAP, UBE2I and Death associated ...
Originally, STAT proteins were described as latent cytoplasmic transcription factors as phosphorylation was thought to be ... Interferon Response Factor) to form ISGF3 (Interferon Stimulated Gene Factor), which binds to the ISRE (Interferon-Stimulated ... There are seven mammalian STAT family members that have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B ... Transcriptional activity and DNA association are determined by the transactivation and DNA-binding domains, respectively. ...
EpoR induced Jak2-Stat5 signaling, together with transcriptional factor GATA-1, induces the transcription of pro-survival ... The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the EPOR gene. EpoR is a 52kDa peptide with a ... Damen JE, Cutler RL, Jiao H, Yi T, Krystal G (Oct 1995). "Phosphorylation of tyrosine 503 in the erythropoietin receptor (EpR) ... as well as the suppression of myeloid/lymphoid transcriptional factors such as PU.1. Direct and significant effects of EpoR ...
However activated GR can complex with these other transcription factors and prevent them from binding their target genes and ... "Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the ... Stöcklin E, Wissler M, Gouilleux F, Groner B (October 1996). "Functional interactions between Stat5 and the glucocorticoid ... "The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy- ...
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth ... Buitenhuis M, Coffer PJ, Koenderman L (2004). "Signal transducer and activator of transcription 5 (STAT5)". Int. J. Biochem. ... Phosphorylation of tyrosine 694 and glycosylation of threonine 92 are important for STAT5a activity. Mutation of serine 710 to ... interacts with chaperones and facilitates protein-protein interactions for transcriptional regulation DNA binding domain (aa331 ...
Once activated, the JAKs create docking sites for the STAT transcription factors by phosphorylation of specific tyrosine ... Cytokine receptors selectively activate particular JAK-STAT pathways to induce transcription of different genes. IL-2 and IL-4 ... Thus IL-2-induced mucosal homeostasis through posttranslational and transcriptional regulation of Jak3. Jak3 is also implicated ... activate JAK1, JAK3 and STAT5. JAK3 activating mutations are found in 16% of T-cell acute lymphoblastic leukemia (T-ALL) ...
Direct binding of transcription factors STAT3 and STAT5 to the Pim-1 promoter results in the transcription of Pim-1. The Pim-1 ... as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1 ... a transcription factor believed to regulate 15% of all genes, and their synergy has been in prostate tumorigenesis. Pim-1 is ... as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1 ...
These include transcription factors that initiate gene expression, kinases that transmit information by post-translationally ... Specific phosphorylation of Hsp90A residues have been shown to occur. These unique phosphorylation sites signal Hsp90A for ... a prolactin-STAT5 target gene identified in breast cancer cells, is involved in apoptosis regulation". Breast Cancer Research ... Lee MO, Kim EO, Kwon HJ, Kim YM, Kang HJ, Kang H, Lee JE (Feb 2002). "Radicicol represses the transcriptional function of the ...
One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in ... "Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic ... GSK3β is negatively controlled by the PI3K pathway in form of phosphorylation, which is one of several ways in which growth ... The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 and Fos which in turn activate the transcription of ...
As a result, an IFN-stimulated gene factor 3 (ISGF3) complex forms-this contains STAT1, STAT2 and a third transcription factor ... in the promoters of certain genes, known as IFN stimulated genes ISGs. Binding of ISGF3 and other transcriptional complexes ... a nuclear adaptor for STAT5 that also regulates signaling through the C3G/Rap1 pathway.[17] Type I IFNs further activate p38 ... and phosphorylation.[19] RIG-G has shown the capacity to inhibit NF-κB and STAT3 signaling in lung cancer cells, which ...
... -CDK4 inhibits pRb through phosphorylation, allowing E2F transcription factors to transcribe genes required for entry ... "Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic ... Inoue K, Sherr CJ (Mar 1998). "Gene expression and cell cycle arrest mediated by transcription factor DMP1 is antagonized by D- ... Cyclin D1-CDK4 also associates with several transcription factors and transcriptional co-regulators. Independent of CDK, cyclin ...
... by tyrosine phosphatase SHP1 through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4 transcription factors ... Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 ... is an enzyme that in humans is encoded by the PTPN6 gene. The protein encoded by this gene is a member of the protein tyrosine ... Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG (March 1994). "Lck-dependent tyrosyl phosphorylation of the ...
... inducing transcription of specific sets of genes. Upregulation of gene expression by STAT5 dimers has been observed for genes ... the phosphorylation occurring at particular tyrosine residues on the C-terminus of the protein; phosphorylation causes STAT5 to ... STAT5 can also form homo-tetramers, usually in concert with the histone methyltransferase EZH2, and act as a transcriptional ... Cytokine Growth Factor Rev. 10 (2): 131-57. doi:10.1016/S1359-6101(99)00011-8. PMID 10743504. Nosaka T, Kawashima T, Misawa K, ...
... inducing transcription of specific sets of genes. Upregulation of gene expression by STAT5 dimers has been observed for genes ... phosphorylation causes STAT5 to dissociate from the receptor;. *the phosphorylated STAT5 finally goes on to form either ... STAT5 can also form homo-tetramers, usually in concert with the histone methyltransferase EZH2, and act as a transcriptional ... Cytokine Growth Factor Rev. 10 (2): 131-57. doi:10.1016/S1359-6101(99)00011-8. PMID 10743504.. .mw-parser-output cite.citation{ ...
... promoting gene transcription.[7][17] Regulation[edit]. Under normal conditions, type I IFN levels are homeostatically regulated ... IFNAR agonism results in transcriptional changes, with the potential to increase or suppress the transcription of over 2000 ... Hertzog PJ, Williams BR (June 2013). "Fine tuning type I interferon responses". Cytokine & Growth Factor Reviews. 24 (3): 217- ... STAT5, and STAT6 may play a role in certain cell types[16]) via their SH2 domains. Once recruited, STAT proteins are ...
... transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon ... is an enzyme that in humans is encoded by the MAPK1 gene. The protein encoded by this gene is a member of the MAP kinase family ... Davis RJ (1995). "Transcriptional regulation by MAP kinases". Mol. Reprod. Dev. 42 (4): 459-67. doi:10.1002/mrd.1080420414. ... "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2 ...
Entrez Gene: MAPK1 mitogen-activated protein kinase 1".. *↑ Ma, Li; Chen Zhenbang; et al. (2005). „Phosphorylation and ... Davis RJ (1996). „Transcriptional regulation by MAP kinases.". Mol. Reprod. Dev. 42 (4): 459-67. PMID 8607977. doi:10.1002/mrd. ... 2000). „Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated ... 2002). „Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a ...
"Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene ... IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I ... "Phosphorylation-induced dimerization of interferon regulatory factor 7 unmasks DNA binding and a bipartite transactivation ... Gene ontology. Molecular function. • DNA binding. • transcription factor activity, sequence-specific DNA binding. • protein ...
Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy |...... upon AKT phosphorylation or RAS-RAF-MAPK signaling and their influence on transcription factor activation by phosphorylation ... by steering transcriptional regulation of important genes relevant for normal or neoplastic cell growth or cell survival. STAT ... This culminates into STAT5 target gene induction and most prominent genes known to be under control of STAT5 signaling in MC ... 78 the major role of STAT5 (like other STATs) is to promote the transcription of different genes. To fulfill this role, STAT5: ...
Gene expression-based discovery of atovaquone as a STAT3 inhibitor and anticancer agent | Blood Journal... a myeloproliferative neoplasm that is frequently driven by activation of STAT3 or the related transcription factor STAT5.6 ... Because STAT3 transcriptional activity is critically dependent on tyrosine phosphorylation, we assayed its status by western ... The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is frequently activated ... Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that has emerged as a key cancer ...
Mammary Gland Factor (MGF) Is a Novel Member of the Cytokine Regulated Transcription Factor Gene Family and Confers the...The mammary gland factor, MGF, has been shown to be a central mediator in the lactogenic hormone response. The DNA binding ... Milk protein gene expression in mammary epithelial cells is regulated by the action of the lactogenic hormones insulin, ... Phosphorylation * Prolactin / metabolism* * Regulatory Sequences, Nucleic Acid * STAT1 Transcription Factor * STAT5 ... Transcription Factors / isolation & purification * Transcription Factors / metabolism * Transcriptional Activation * Tyrosine ...
The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent | Molecular Cancer Therapeutics... they inhibit phosphorylation of signal transducers and activators of transcription (STAT) transcription factors (17, 18), which ... the triterpenoids enhance the transcriptional activity of the respective Smads that are involved in regulating gene activity. ... as mediated by the ability of both CDDO-Me and CDDO-imidazolide to suppress the phosphorylation of both STAT3 and STAT5, which ... 11-14); (d) they inhibit activity of the transcription factor nuclear factor-κB by directly inhibiting its activating kinase, I ...
Deletion of the carboxyl-terminal transactivation domain of MGF-Stat5 results in sustained DNA binding and a dominant negative...The Stat (signal transducer and activator of transcription) factors transmit cytokine, growth factor, and hormone responses. ... Two closely related variants of Stat5, Stat5a and Stat5b, are encoded by distinct genes. We examined the functional properties ... Coexpression of Stat5a or Stat5b and of the carboxyl-terminal deletion mutants resulted in the suppression of transcriptional ... Upon prolactin activation, tyrosine phosphorylation and the specificity of DNA binding were indistinguishable among the three ...
JCI -
Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failureTNK1 expression results in phosphorylation and activation of transcription factor STAT3. (C) Representative images of small and ... we performed comparative genome-wide transcriptional profiling followed by gene set enrichment analysis. We identified a set of ... but not of STAT1 or STAT5 (Supplemental Figure 3, E and F). We could further demonstrate that STAT3 phosphorylation is a direct ... Novel antiviral host factor, TNK1, regulates IFN signaling through serine phosphorylation of STAT1. Proc Natl Acad Sci U S A. ...
Role of STAT3 in Cancer Metastasis and Translational Advances... a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway," Cell, ... Phosphorylation of this serine residue is required for maximal transcriptional activity [7, 8]. ... atiprimod inhibits proliferation and induces apoptosis by suppressing STAT3 and STAT5 phosphorylation [138]. ... STAT family proteins are latent cytoplasmic transcription factors initially discovered as acute phase response factors in 1994 ...
Frontiers | Transcriptional, Epigenetic and Pharmacological Control of JAK/STAT Pathway in NK Cells | ImmunologySeveral soluble factors and cytokines regulate the distinct stages of NK cell differentiation, and ultimately, their functional ... Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) ... technology have led to unravel novel molecular aspects of gene regulation, with the aim to provide genomic views of how STATs ... Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) ...
Hypoxia/geneticsSTAT proteins act as transcription factors activated by phosphorylation on its tyrosine residues upon stimulation by various ... STAT5 recognizes the interferon-gamma activated site TTCNNNGAA (GAS sequence) in the promoter region of the beta-casein gene. ... it is essential to gain insights in the formation and regulation of HIF transcriptional machineries related to angiogenesis. ... The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In ...
STAT proteins act as transcription factors activated by phosphorylation on its tyrosine residues upon stimulation by various ... STAT5 recognizes the interferon-gamma activated site TTCNNNGAA (GAS sequence) in the promoter region of the beta-casein gene. ... These data suggest that STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation. ... Phosphorylation , Protein-Serine-Threonine Kinases/metabolism , Transcription Factors/genetics , Up-Regulation ...
5B), while the transcriptional activity of a non-calcium-responsive transcription factor, AP-1, was not affected (Fig. 5C). ... transduction of primary lymphocytes with a retrovirus vector expressing p12I causes a modest increase in Stat5 phosphorylation ... Wu and Marsh (53) recently reported that HIV infection leads to selective transcription of the nef and tat genes before ... We recently reported that p12I expression induces the calcium-responsive T-cell transcription factor, nuclear factor of ...
In contrast, AKT phosphorylation induced by insulin-like growth factor-I remained unchanged, showing selectivity of the ... ultimately resulting in transcriptional regulation of specific genes that mediate cellular responses. ... and suppression of these transcription factors leads to apoptosis. Blood 2004;103:3175-84. ... Importantly, TEL-JAK2 transgenic mice develop T-cell leukemia with constitutive activation of STAT1 and STAT5 in leukemic ...
STAT transcription factor, all-alpha domain (IPR013800) | InterPro | EMBL-EBI... family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter ... The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to ... Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation. ... suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional ...
Anti-phospho-STAT5A/B (Ser726/Ser731) Antibody | 06-867... activator of transcription 5A/B & has been tested in WB. Find MSDS or SDS, a COA, data sheets and more information. ... Transcription factors of the Stat gene family are selectively activated by many hormones and cytokines. Stat5 originally was ... Finally, phosphorylation of the PSP motif of Stat5a or Stat5b was not essential for DNA binding or transcriptional activation ... Entrez Gene Summary. The protein encoded by this gene is a member of the STAT family of transcription factors. In response to ...
GFI1 (growth factor independent 1 transcription repressor)... growth factor independent 1 transcription repressor), Authors: Tarik Möröy, Cyrus Khandanpour. Published in: Atlas Genet ... The molecular function of Gfi1 is that of a DNA-binding transcriptional repressor. A target gene sequence has been defined ( ... and subsequently the phosphorylation of STAT5, which is an important downstream signaling molecule in the IL-7R pathway. While ... transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II DNA-binding transcription factor ...
Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors ISGF3, a heterotrimer ... Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contribute to transcriptome changes in ... metabolic functions of IRF9 as well as the regulation of NK cell activity by kinase-dead TYK2 and different phosphorylation ... Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors ISGF3, a heterotrimer ...
The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance | The Journal of Immunology25) have reported that, based on patterns of STAT-5 phosphorylation, the responsiveness of human thymocytes to IL-7 was at ... IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORγt: impact on thymocyte development. J. ... The human gene for IL-7 resides on chromosome 8q12-13 and shares 81% homology with murine coding regions. IL-7 is a member of ... T cells through activation of the transcriptional repressor, GFI1 (64). IL-7Rα down-regulation contributes to maintenance of ...
Cytokine-Induced IL-10 Manifestation Is usually Regulated by Stat3 and Stat5. Stat transcription factors regulate and genes ... Increased Stat3 phosphorylation in SLE T cells enhances its recruitment to regulatory elements and the replacement of Stat5 at ... To investigate effects of Stat3 and Stat5 on promoter ?741 and ?149 base pairs upstream of the transcriptional start site (SRE- ... In SLE T cells, reduced DNA methylation allows for transcription-factor recruitment. Both Stat3 and Stat5 promoter and the I- ...
The protein encoded by this gene belongs to the ETS family of transcription factors. There are 28 ETS genes in humans and 27 ... Such phosphorylation of ETS1 alters its target gene repertoire. The Ku80 portion of DNA-PK, acting alone, interacts with ETS1 ... Dwyer J, Li H, Xu D, Liu JP (Oct 2007). "Transcriptional regulation of telomerase activity: roles of the Ets transcription ... AP1, STAT5 and VDR bind to C-terminal domain. Also, ETS1 has been shown to interact with TTRAP, UBE2I and Death associated ...
To date, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling has been proposed to be crucial in ... The STAT3 transcription factor is then activated through phosphorylation by JAKs. Active STAT3 then binds the p300/CBP ... which specifies glial cell fate by transcriptional activation of astrocytic genes, such as Gfap and S100β. However, STAT3 can ... Interestingly, STAT5 in the striatum showed a reverse expression pattern. Furthermore, STAT5 has been shown to be weakly ...
![Anti-STAT5a antibody [E289] Recombinant (ab32043) | Abcam](data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAABAAAAAQCAMAAAAoLQ9TAAAAA3NCSVQICAjb4U/gAAAAP1BMVEVuenpxfH10gIFjcXJpdXVodHRuenpueHpveXtoc3T////v8PBrd3iEjY3Q09NSY2XZ29v7+/u8wMCdo6RSY2S+t2czAAAACnRSTlOl////a2yprahm3N6WhQAAAGVJREFUGJV1j8cCwCAIQ1E6bMDR8f/fWq0eakcOHB4EAi2ObnILOdtpIrKmSK9qLFXAfjesqg2oFwAbsHKbACRktoYKOCBFjgkSq4UFvuyD8B/IluNuyb1+6cfZZ7A++uu5Ye40nqfSBUbHLeVnAAAAAElFTkSuQmCC)
Anti-STAT5a antibody [E289] Recombinant (ab32043) | AbcamSerine phosphorylation is also required for maximal transcriptional activity.. * Cellular localization. Cytoplasm. Nucleus. ... Belongs to the transcription factor STAT family.. Contains 1 SH2 domain.. * Post-translational. modifications ... Entrez Gene: 6776 Human. *Entrez Gene: 20850 Mouse. *Entrez Gene: 24918 Rat ... Carries out a dual function: signal transduction and activation of transcription. Binds to the GAS element and activates PRL- ...
Transcription factor regulation of CD8+ T-cell memory and exhaustion. Immunol. Rev. 236: 167-175. ... T cells from HIV-infected patients display defective stimulation-induced phosphorylation of Stat5, ERK1/2, and p38, but ... Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and ... Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. ...
Reduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: Reversal by growth hormone | PNASGH signals by inducing phosphorylation of the transcription factor STAT-5 (21). Immunoblotting revealed elevated phospho-STAT-5 ... Two closely related genes, LC3A and LC3B, encode LC3-I and LC3-II (20). To determine whether the difference in LC3-II in the ... liver of WT and Goat−/− mice was the result of transcriptional changes in LC3A and/or LC3B, we checked their mRNA expression ... The plot reveals a strong correlation between LC3-II level and p-STAT5 level (R2 = 0.90). Inasmuch as p-STAT5 is produced by GH ...
Development - Prolactin receptor signaling Pathway Map - PrimePCR | Life Science | Bio-RadSelect your gene target of interest using an interactive pathway map, and select your plate. ... determining the milk protein gene transcription [3], [18].. STAT5 factors also induce the transcription of Cyclin D1 (which ... factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription ... Integrin-mediated tyrosine phosphorylation of Shc in T cells is regulated by protein kinase C-dependent phosphorylations of Lck ...
... are a family of cytoplasmic latent transcription factors that are activated… ... After phosphorylation by JAK tyrosine kinases, STATs enter the nucleus to regulate transcription of many different genes. Among ... STAT5 has been shown to be the essential mediator of prolactin induced milk protein gene activation. ... STAT5b may also act as a transcriptional inhibitor as demonstrated by inhibition of NF-kB mediated signaling. This STAT5b- ...
RegulationStatStat3 and Stat5InhibitionInduceDownstreamPromotersStat5a and Stat5bActivatorMammary epithelial cellsStat5bKinaseMolecularProlactinRepressorProliferationEpithelialCytokines and growth factorsRegulate geneTargetSTAT6InhibitorDimerizationActivityAssaysTargetsCellularCellsReceptorsNuclear translocationGrowthP300DimersTransactivationCytokineStimulationSTAT1 and STAT2SequencesPathwayTransducers
- Here, we discuss how the recent advances of next generation sequencing (NGS) technology have led to unravel novel molecular aspects of gene regulation, with the aim to provide genomic views of how STATs regulate transcriptional and epigenetic features of NK cells during the different functional stages. (frontiersin.org)
- Other mechanisms that may lead to increased JAK activation include gene amplification, phosphorylation by oncogenic tyrosine kinases, increased growth factor production, and disruption of normal negative regulation. (aacrjournals.org)
- These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1. (frontiersin.org)
- However, specific transcriptional cofactors and mechanisms used by Stat6 to mediate target gene regulation or specificity under physiological conditions are poorly understood. (pnas.org)
- These results provide the first evidence for transcriptional regulation of the immunomodulatory peptide hormone PRL by NR4A2 in synoviocytes, and highlight a novel molecular pathway in inflammatory arthritis. (biomedcentral.com)
- However, given the up-regulation of several STAT3 transcriptional targets following treatment, further investigation of STAT3 and its related signaling pathways in OSCC is warranted. (springer.com)
- STATs participate in oncogenesis through up-regulation of genes encoding apoptosis inhibitors and cell cycle regulators such as Bcl-x L , Mcl-1, cyclins D1/D2, and c-Myc. (aacrjournals.org)
- In the past few years, our understanding of the nutritional, hormonal and particularly transcriptional regulation of lipogenesis has expanded greatly. (embopress.org)
- In this study, we characterise the regulation of inflammation-related genes by leptin in insulinoma cells and compare the effect of transcriptional regulation by leptin with that of other cytokines. (biomedcentral.com)
- Reporter gene assays showed that leptin induced the expression of preprotachykinin-1 and lipocalin-2 on the level of promoter regulation. (biomedcentral.com)
- The half-lives of Myc mRNA and protein are short, allowing for tight and rapid regulation of Myc levels, which occurs via numerous transcription factors (TFs) and signaling pathways. (biomedcentral.com)
- To provide some insight into the complexity of Myc regulation, we will mention a few of the factors and pathways that impact on its expression, many of which were shown to be essential during mammary gland development [ 4 ]. (biomedcentral.com)
- This analysis revealed a massive response to EGFR inhibition already within the first 24 h, including significant regulation of hundreds of genes known to control downstream signaling, such as transcription factors, kinases, phosphatases and ubiquitin E3-ligases. (mcponline.org)
- Promoters provide the obligatory transcriptional start sites necessary for RNA synthesis and are often sites of signal-dependent regulation ( Figure 1 ). (jci.org)
- In contrast, s80 isoforms have entirely novel signaling functions in transcriptional regulation. (sciencemag.org)
- Here, we measured Myc‐induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript‐specific regulation of protein translation. (uni-wuerzburg.de)
- Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. (uni-wuerzburg.de)
- Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. (uni-wuerzburg.de)
- STATs are activated through tyrosine phosphorylation, mainly by JAK kinases, which results in their dimerization, nuclear translocation and regulation of gene expression. (merckmillipore.com)
- Triggering these cosignaling downstream pathways ultimately leads to the transcriptional activation and mRNA stabilization of genes encoding a number of cytokines critically involved in the regulation of Th1-Th2 differentiation ( 8 ). (asm.org)
- In addition, the potential of epigenetic regulation (non-sequence inheritable chemical changes in chromatin, such as DNA methylation and histone modifications, which affect gene expression) to manipulate mammary function is emerging. (springer.com)
- When the GR binds to glucocorticoids, its primary mechanism of action is the regulation of gene transcription. (wikidoc.org)
- Work in his group also demonstrated that PKB-mediated phosphorylation of Forkhead transcription factors (FOXO) was critical for the regulation of leukocyte proliferation and survival. (umcutrecht.nl)
- Current literature suggests that NADPH oxidase activity may modulate adaptive immune responses via ROS signaling of cytokine gene expression and regulation of the efficient antigen presentation for T cell activation and proliferation , , though the cell type involved in NADPH oxidase-mediated regulation of adaptive immunity are not fully detailed. (prolekare.cz)
- FGF1 regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of the MAPK pathway. (uni-wuerzburg.de)
- In this study, we analyzed leptin-mediated signal transduction and preproinsulin gene regulation at the molecular level in pancreatic β-cells. (diabetesjournals.org)
- Studies such as those undertaken on STATs have paved the way for future research into transcriptional regulation as we try to better understand the molecular basis of disease (3). (promegaconnections.com)
- Developmental and environmental regulation of a mammary gland-specific nuclear factor essential for transcription of the gene encoding beta-casein. (semanticscholar.org)
- However, PU.1 down-regulation is specifically required for progression in the T cell lineage ( 22 ), and another Ets factor, GA binding protein (GABP), was shown to regulate IL-7Rα expression in T cells ( 23 ). (rupress.org)
- RhoH is a GTPase deficient protein [ 7 , 8 ] and its activity is presumably modulated through transcriptional regulation [ 7 ]. (pubmedcentralcanada.ca)
- In male rodents, activation of the leptin receptor modulates a cascade of intracellular signal transduction pathways which may lead to regulation of transcription factors having influences on steroidogenesis in Leydig cells. (deepdyve.com)
- Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1. (semanticscholar.org)
- Dr. Sakamoto?s research has focused on signaling pathways and gene regulation in normal and aberrant hematopoiesis, including leukemia and bone marrow failure syndromes. (stanford.edu)
- Notably, in breast cancer cells, progestin-bound PRs induce rapid MAPK activation leading to selective regulation of growth-promoting genes by phosphorylated PR species. (datamed.org)
- mCD PR failed to undergo ligand-induced phosphorylation on Ser81, a ck2-dependent site required for progestin-regulation of select growth-promoting genes (BIRC3, HSD11β2, HbEGF). (datamed.org)
- Co-regulation of select target genes by phospho-Ser81 PR and phospho-STAT5 is likely a global mechanism required for the activation of growth promoting programs active during normal mammary gland development and relevant to mechanisms of breast cancer progression. (datamed.org)
- One of the mechanisms of NMI action in breast cancer was implied in its ability to negatively modulate transcriptional regulation of target genes by c-Myc. (biomedcentral.com)
- The Stat (signal transducer and activator of transcription) factors transmit cytokine, growth factor, and hormone responses. (asm.org)
- Seven members of the Stat gene family are known. (asm.org)
- Phosphorylation of specific tyrosine residue is an essential step for STAT activation. (hindawi.com)
- Once activated, STAT dimerizes to other STATs by reciprocal SH2 phosphotyrosine interaction, leading to its translocation into the nucleus followed by its binding to the specific enhancer elements for initiation of transcription [ 2 , 3 ] (Figure 1 ). (hindawi.com)
- Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway control distinct aspects of NK cell biology, ranging from development, terminal differentiation, activation, and generation of cells with adaptive properties. (frontiersin.org)
- In particular, cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway control NK cell development, terminal differentiation, acquisition of effector phenotype up to generation of cells with adaptive features able to provide secondary responses ( 16 , 17 ). (frontiersin.org)
- Activation of the JAK tyrosine kinases occurs upon receptor engagement, and the juxtaposition of JAKs and STATs allows, after phosphorylation, STAT dimers to dissociate from the membrane complex and to migrate into the nucleus, where they bind specific DNA-motifs modulating gene expression ( 20 ). (frontiersin.org)
- The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus [ PMID: 12039028 ]. (ebi.ac.uk)
- The phosphorylated STAT molecules then form homo- or heterodimers through SH2-mediated interaction and translocate into the nucleus to activate the transcription of various target genes. (bvsalud.org)
- The protein encoded by this gene is a member of the STAT family of transcription factors. (merckmillipore.com)
- In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. (merckmillipore.com)
- SwissProt: P42229 ## Belongs to the transcription factor STAT family. (merckmillipore.com)
- Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. (frontiersin.org)
- Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. (frontiersin.org)
- Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. (frontiersin.org)
- Activated receptor through JAK2 recruits Signal transducers and activators of transcription (STAT ), in particular STAT1 , STAT3 and STAT5 ( STAT5A and STAT5B ), and stimulates STAT s tyrosine phosphorylation. (bio-rad.com)
- In response to Prolactin receptor stimulation activated STAT s translocate into the nucleus and bind to the interferon-gamma activation sequence (GAS) in the promoter region of target genes. (bio-rad.com)
- Acris Antibodies offers a wide range of antibodies to STAT Transcription Factors. (acris-antibodies.com)
- Fig.1: Induction of phosphorylation of STAT 1 at Ser727 in human malignant melanoma cells (short-term culture derived from a patient) in response to interferons. (acris-antibodies.com)
- Seven mammalian STAT genes have been identified in three chromosomal clusters ( 4 ). (sciencemag.org)
- Phosphorylation on a single tyrosine located around residue 700 in each protein is obligatory for STAT activation ( 1 , 2 ) (Fig. 1 ). (sciencemag.org)
- Phosphorylation of the kinase is the first of three tyrosine phosphorylations culminating in STAT activation (Fig. 2 ). (sciencemag.org)
- The alpha subunit binds ligand and plays a critical role in activating the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway. (ashpublications.org)
- Both butyrate and specific growth-stimulatory SCFADs induced prolonged signal transducer and activator of transcription (STAT)-5 phosphorylation and activation, and c-cis expression, persisting for more than 120 minutes, whereas with IL-3 alone phosphorylation disappeared within minutes. (elsevier.com)
- The signal transducers and activators of transcription (STAT)factors function as downstream effectors of cytokine and growth factor receptor signaling. (aacrjournals.org)
- Members of the signal transducer and activator of transcription (STAT) protein family are intracellular transcription factors that mediate many aspects of cellular immunity, proliferation, apoptosis and differentiation. (wikipedia.org)
- Extracellular binding of cytokines or growth factors induce activation of receptor-associated Janus kinases, which phosphorylate a specific tyrosine residue within the STAT protein promoting dimerization via their SH2 domains. (wikipedia.org)
- Once STAT reaches the nucleus, it binds to a consensus DNA-recognition motif called gamma-activated sites (GAS) in the promoter region of cytokine-inducible genes and activates transcription. (wikipedia.org)
- These data have important implications for human cancer: They suggest new drug therapies, which could target the noncanonical functions of JAK and STAT. In this article, we discuss how the canonical arm of the JAK‐STAT pathway functions in tumourigenesis, focussing on JAK and on STAT1, STAT3 and STAT5. (els.net)
- Activated JAK phosphorylates STAT . Phosphorylated STAT dimerises and translocates to the nucleus to bind sequences in the target gene promoters. (els.net)
- Dimeric STAT binding results in gene transcription. (els.net)
- Albasanz‐Puig A, Murray J, Namekata M and Wijelath ES (2012) Opposing roles of STAT‐1 and STAT‐3 in regulating vascular endothelial growth factor expression in vascular smooth muscle cells. (els.net)
- 2006) The genes induced by signal transducer and activators of transcription (STAT)3 and STAT5 in mammary epithelial cells define the roles of these STATs in mammary development. (els.net)
- Classen AK, Bunker BD, Harvey KF, Vaccari T and Bilder D (2009) A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK‐STAT signaling. (els.net)
- The leptin receptor (LEPRb) is a class I cytokine receptor that mediates activation of STAT transcription factors. (biomedcentral.com)
- Ligand binding to LEPRb results in trans-autophosphorylation and thereby activation of the receptor-associated tyrosine kinase JAK2 and subsequent recruitment and activation of STAT factors to phosphorylated tyrosine residues in the cytoplasmic part of LEPRb [ 10 , 14 ]. (biomedcentral.com)
- The myc promoter contains TF binding sites for Myc (auto-suppression), estrogen receptor (ER) alpha, T-cell factor (TCF) 4, Notch/C promoter-binding factor 1 (Cbf1), E2F, Fos/Jun, signal transducer and activator of transcription (Stat) 3, NF-κB, Smads and others. (biomedcentral.com)
- The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway mediates important responses in immune cells. (nih.gov)
- Activation of any of the four JAK family members leads to phosphorylation of one or more of seven STAT family members. (nih.gov)
- Phosphorylation of STAT family members leads to their dimerization and translocation into the nucleus, in which they bind specific DNA sequences to activate gene transcription. (nih.gov)
- We identify a direct cooperation between STAT5 and HOXA9 at the transcriptional level and identify PIM1 kinase as a possible drug target in mutant JAK/STAT/HOXA9-positive leukemia cases. (aacrjournals.org)
- STAT Transcription Factors: Controlling All Aspects of NK Cell Biology / Eva Maria Putz, Eva Zebedin and Veronika Sexl -- Function of JAKs and STATs in Lymphocytes: Bench to Bedside / Alejandro Villarino, Xiang-Ping Yang, Kiyoshi Hirahara, Yuka Kanno and John J. O' Shea, et al. (stanford.edu)
- ASCs favored STAT3 over STAT5 transcription factor binding on STAT binding sites within the IL-17A/F gene locus. (diabetesjournals.org)
- Many cytokines, hormones, and growth factors activate Janus kinases to tyrosine phosphorylate select members of the Stat transcription factors. (unimi.it)
- We supply the proof exhibiting cyclin D1 might be modulated by STAT3 induced by EBV LMP1, illustrating the importance of the JAK STAT signaling pathway on EBV LMP1 induced cyclin D1 transcription and expression. (srcsignaling.com)
- Signal transducers and activators of transcription (STAT) family are critical transcription factors, which have been proved as prognostic predictors for a number of cancers. (bioscirep.org)
- Signal transducers and activators of transcription (STAT) are cytoplasmic transcription factors including a total of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6) [ 4 ]. (bioscirep.org)
- In the present study, we mined the 'Kaplan-Meier plotter' (KM plotter) online database to comprehensively explore the prognostic values of seven STAT genes in breast cancer patients. (bioscirep.org)
- JAK1/JAK2 or TYK2 signaling then lead to the stimulation of members of the STAT family ( STAT1 , STAT3 , STAT5 , STAT6 ). (bio-rad.com)
- Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 β-cells. (diabetesjournals.org)
- In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic β-cells. (diabetesjournals.org)
- Leptin signal transduction occurs through a distinct receptor of the class 1 cytokine superfamily of receptors ( 9 ), which is intracellularly coupled to the janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway ( 10 ). (diabetesjournals.org)
- Subsequently, transcription factors of the STAT family are recruited to the receptor and also phosphorylated. (diabetesjournals.org)
- The activated STAT dimer then translocates to the nucleus and binds to a STAT consensus DNA element, resulting in gene transcription. (biomedcentral.com)
- Just recently for example one scientist drew my attention to a couple of papers about a family of mammalian transcription factors called STAT (short for S ignal T ransducers And A ctivators Of T ranscription). (promegaconnections.com)
- Signal transducer and activator of transcription (STAT) activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. (biomedcentral.com)
- However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. (biomedcentral.com)
- Thus, as a result of high leptin levels interacting with its receptor and modulating the activity of the JAK/STAT signaling pathway, the activity of transcription factors important for steroidogenic genes expressions may be inhibited in Leydig cells. (deepdyve.com)
- Our results suggest that STAT transcriptional activity is downregulated by high levels of leptin, leading to reduced cAMP-dependent steroidogenic genes (Star and Cyp11a1) expressions in MA-10 Leydig cells. (deepdyve.com)
- Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2 . (rcsb.org)
- Inhibition of JAK/STAT signaling blocked progestin-induced STAT5 and Wnt1 expression. (datamed.org)
- NMI has been shown to augment STAT-mediated transcription in response to cytokines, specifically by mediating association of co-activator protein CBP/p300 with STAT1 or STAT5 [ 3 ]. (biomedcentral.com)
- Stat3 and Stat5) is associated with cellular transformation. (ebi.ac.uk)
- Persistent signaling of specific STATs, in particular Stat3 and Stat5, has been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis. (aacrjournals.org)
- In particular, STAT3 and STAT5 are known to bind to PIM1 promoter, upregulating its transcription [ 13 , 14 ]. (jcancer.org)
- Activation of STAT3 and STAT5 was partially blocked by RGFP966 at 2 h after LPS-stimulation. (hindawi.com)
- Inhibition of phosphorylation of these targets has proven their crucial role in disease-evolution in both malignancies. (haematologica.org)
- This can be assayed either by measuring inhibition of endothelial cell growth and invasion in cell culture or, more meaningfully, in vivo as by evaluating suppression of vascularization of Matrigel plugs containing angiogenic growth factors. (aacrjournals.org)
- 1 μmol/L). Growth suppression of INA-6 correlated with an increase in the percentage of apoptotic cells and inhibition of signal transducer and activator of transcription 3 phosphorylation. (aacrjournals.org)
- STAT5b may also act as a transcriptional inhibitor as demonstrated by inhibition of NF-kB mediated signaling. (acris-antibodies.com)
- Exposure of SCCF2 cells to LLL12 resulted in decreased expression of pSTAT3 and total STAT3, apoptosis as assessed by caspase 3/7 activation, inhibition of colony formation and reduced expression of the STAT3 transcriptional target survivin. (springer.com)
- The OSCC cell lines with low basal STAT3 phosphorylation did not exhibit these effects, suggesting that STAT3 inhibition was responsible for the observed results. (springer.com)
- S6 is activated downstream of mTOR, and additional inhibition of mTOR or S6K1 reduced S6 phosphorylation and resensitized PI3KCA E545K cells to MEKi plus CDK4i. (aacrjournals.org)
- Pharmacological inhibition of EGFR activity or SREBP-2 activity suppressed the NRG1-mediated induction of cholesterol synthesis-related genes. (sciencemag.org)
- Pharmacological inhibition of the activity of SREBP site 1 protease or of all EGFR family members (with lapatinib), but not EGFR alone (with erlotinib), impaired NRG1-induced expression of cholesterol biosynthesis genes. (sciencemag.org)
- Onset of lactation in the bovine mammary gland: gene expression profiling indicates a strong inhibition of gene expression in cell proliferation. (springer.com)
- Finally, conditioned media from activated ASC-MNC cocultures inhibited adipocyte differentiation mRNA markers and impaired insulin-mediated Akt phosphorylation and lipolysis inhibition. (diabetesjournals.org)
- This inhibition occurred at the transcription factor level. (ubc.ca)
- Several senescence-associated factors were found to be transcribed and secreted in response to BRAF or MEK inhibition, among them members of the fibroblast growth factor family. (uni-wuerzburg.de)
- We identified the growth factor FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro-apoptotic effects of the drug and activates fibroblasts to secrete HGF. (uni-wuerzburg.de)
- 9AA treatment resulted in inhibition of HIV LTR transcription in a specific manner that was highly dependent on the presence and location of the amino moiety. (biomedcentral.com)
- 9AA inhibited viral replication in both p53 wildtype and p53 mutant cells, indicating that there is another p53 independent factor that was critical for HIV inhibition. (biomedcentral.com)
- Furthermore, we observed p21WAF1 in complex with cyclin T1 and cdk9 in vitro , suggesting a direct role of p21WAF1 in HIV transcription inhibition. (biomedcentral.com)
- The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells. (merckmillipore.com)
- STAT5 factors also induce the transcription of Cyclin D1 (which regulates cell cycle progression) and the antiapoptotic factor BCL2-like 1 ( Bcl-XL ) [ 19 ], [ 20 ]. (bio-rad.com)
- STAT1 deficient knock-out mice are unable to induce IFN regulated genes and are extremely susceptible to viral diseases. (acris-antibodies.com)
- Inflammatory arthritis is driven by pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and prostaglandin E 2 (PGE 2 ) that induce synovial hyperplasia and trigger the erosion of cartilage and bone. (biomedcentral.com)
- Investigation of potential mechanisms of action of these SCFADs demonstrates that these compounds induce prolonged expression of the growth-promoting genes c-myb and c-myc. (elsevier.com)
- Once activated, STATs induce the expression of specific target genes that control critical cellular processes. (dana-farber.org)
- This observation is in agreement with other reviews that nuclear EGFR interacts with transcription components, such as STAT3, E2F1, STAT5 and TIF2 to induce the expression of some target genes in numerous cancers. (srcsignaling.com)
- Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. (frontiersin.org)
- S6 is downstream of mTOR, and treatment with an mTORC inhibitor reduced S6 phosphorylation and suppressed the growth of MEKi/CDK4/6i-resistant tumors in vivo . (aacrjournals.org)
- Considering the large number of receptors, hormones, paracrine factors and other signaling molecules that can impact on Myc levels, it is likely that Myc has a variety of functions throughout normal mammary gland development, downstream of one or more of these inputs. (biomedcentral.com)
- An important regulator of mast cells, STAT5, is activated downstream of the receptors for immunoglobulin E, interleukin-3 and stem cell factor. (nih.gov)
- We confirmed mechanistically that WW-domain containing transcription regulator-1 ( WWTR1 ) gene was a downstream target of miR-550-1. (ijbs.com)
- We propose that Stat5a delta 750 and Stat5b delta 754 are lacking functional transactivation domains and exert their dominant negative effects by blocking the DNA-binding site in Stat5-responsive gene promoters. (asm.org)
- Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. (uni-wuerzburg.de)
- The tyrosine‐phosphorylated STAT6 forms dimers that are translocated to the nucleus, where they bind to specific recognition sequences in the promoters of IL‐4‐responsive genes. (embopress.org)
- As Dana Farber molecular biologist Erik Nelson and his group have shown through their own experiments, STATs can bind to sequences tens of thousands of base pairs away from the gene promoters that they regulate (2). (promegaconnections.com)
- MGF-binding sites are present in the promoters of the most abundantly expressed milk protein genes. (semanticscholar.org)
- Forms preferably ternary complexes with BCOR and SMRT/ NCOR2 on target gene promoters but, on enhancer elements, interacts with SMRT/ NCOR2 and HDAC3 to repress proximal gene expression. (rcsb.org)
- Binding of Rho- and actin-regulated MRTF:SRF complexes to target gene promoters requires an SRF-binding site only, whereas MAPK-regulated TCF:SRF complexes in addition rely on flanking sequences present in the serum response element (SRE). (biomedcentral.com)
- Two closely related variants of Stat5, Stat5a and Stat5b, are encoded by distinct genes. (asm.org)
- The genes encoding STAT1 and STAT4 are located on chromosome 2, STAT2 and STAT6 on chromosome 17, and STAT3, STAT5a, and STAT5b on chromosome 12. (hindawi.com)
- The present study set out to establish whether Stat5a and Stat5b are under the control of an interleukin-2 (IL2)-activated Stat5 serine kinase. (unimi.it)
- We now report that IL2 stimulated marked phosphorylation of serine and tyrosine residues of both Stat5a and Stat5b in human T lymphocytes and in several IL2-responsive lymphocytic cell lines. (unimi.it)
- The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is frequently activated inappropriately in a wide range of hematological and solid cancers, but clinically available therapies targeting STAT3 are lacking. (bloodjournal.org)
- Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. (hindawi.com)
- Studies designed to investigate the mechanism of these immortalization and transformation events have been primarily focused on Tax, a pleiotropic viral and cellular transcriptional activator encoded by pX open reading frame (ORF) IV ( 26 , 39 , 42 , 55 ). (asm.org)
- Anti-phospho-STAT5A/B (Ser726/Ser731) Antibody is a rabbit polyclonal antibody for detection of phospho-STAT5A/B (Ser726/Ser731) also known as signal transducer & activator of transcription 5A/B & has been tested in WB. (merckmillipore.com)
- By using this novel peptide substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A) in CR prostate cancer. (plos.org)
- The transcriptional activity of PRRI can be regulated by the viral protein Tax (transcription activator protein of human T-cell leukemia virus type 1), and the transcription factors NF-κB and a serum response factor-related protein ( 2 , 30 , 35 , 47 ). (asm.org)
- STAT5B (Signal Transducer And Activator Of Transcription 5B) is a Protein Coding gene. (genecards.org)
- OSM-induced plasticity was Signal Transducer and Activator of Transcription 3 (STAT3)-dependent, and also required a novel intersection with transforming growth factor-β (TGF-β)/SMAD signaling. (pubmedcentralcanada.ca)
- The transcription factor STAT3 (signal transducer and activator of transcription 3) is frequently activated in tumor cells. (readbyqxmd.com)
- Signal transducer and activator of transcription 1 (STAT1), a transcription factor known to participate in antiviral responses, acts as a tumor suppressor inhibiting cell growth and promoting apoptosis. (readbyqxmd.com)
- Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. (mdpi.com)
- The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that, when dysregulated, becomes a powerful oncogene found in many human cancers, including diffuse large B-cell lymphoma. (g3journal.org)
- The replication and transcription activator of murine gammaherpesvirus 68 cooperatively enhances cytokine-activated, STAT3-mediated gene expression. (nih.gov)
- Milk protein gene expression in mammary epithelial cells is regulated by the action of the lactogenic hormones insulin, glucocorticoids and prolactin. (nih.gov)
- These results showed that DFO or hypoxia induces tyrosine phosphorylation of STAT5a and also increases the binding activity of STAT5a DNA in mammary epithelial cells. (bvsalud.org)
- Prolactin is a primary factor required for the growth and terminal differentiation of mammary epithelial cells as determined by the induction of transcription of milk protein genes required for lactation [ 2 ], [ 3 ]. (bio-rad.com)
- Overexpressing ERBB4 in cultured mammary epithelial cells or adding the ERBB4 ligand neuregulin 1 (NRG1) to breast cancer cell cultures promoted the expression of genes regulated by YAP, such as CTGF . (sciencemag.org)
- Coexpression of Stat5a or Stat5b and of the carboxyl-terminal deletion mutants resulted in the suppression of transcriptional induction in COS or Ba/F3 cells. (asm.org)
- Interestingly, IL2-induced serine phosphorylation of Stat5a differed quantitatively and temporally from that of Stat5b with Stat5a serine phosphorylation leveling off after 10 min and the more pronounced Stat5b response continuing to rise for at least 60 min of IL2 stimulation. (unimi.it)
- Luciferase reporter assays were used to measure Brk-induced STAT5b transcriptional activity. (biomedcentral.com)
- Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that Brk specifically mediated STAT5b phosphorylation at the activating tyrosine, Y699. (biomedcentral.com)
- Transient transfection of Brk into the Brk-negative BT-549 breast cancer cell line enhanced STAT5b transcriptional activity, as measured by a STAT5-specific luciferase reporter. (biomedcentral.com)
- Furthermore, overexpression of kinase active c-Src enhanced Brk-induced STAT5b transcriptional activity. (biomedcentral.com)
- Our studies demonstrate that Brk phosphorylates STAT5b on Y699, leading to increased STAT5b transcriptional activity. (biomedcentral.com)
- Ligand-activated receptors that catalyze this phosphorylation include receptors with intrinsic tyrosine kinase activity [for example, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and colony-stimulating factor-as well as receptors that lack intrinsic tyrosine kinase activity but to which Janus kinases (JAKs) are noncovalently associated ( 3 , 6 ). (sciencemag.org)
- In summary, optimal JAK kinase activity is a critical determinant of normal transmission of cytokine and growth factor signals. (nature.com)
- Molecular cloning of cytokine receptors and subsequent structure-function studies has revealed that unlike growth-factor receptors, cytokine receptors lack a cytoplasmic kinase domain. (nature.com)
- PI3KCA E545K expression conferred resistance to MEKi plus CDK4i in NRAS-mutant melanoma cell lines and increased phosphorylation of S6 and its upstream kinase S6K1. (aacrjournals.org)
- When Akt transiently associates with Inhibitor of nuclear factor kappa B kinase catalytic subunits ( IKK ), it phosphorilates and activates IKK . (bio-rad.com)
- Several known individual molecular targets of CDDO-Me and related triterpenoids that are relevant to all of these findings include nuclear factor-κB signaling, signal transducers and activators of transcription signaling, and transforming growth factor-β signaling, as well as Keap1, the endogenous inhibitor of the transcription factor Nrf2. (aacrjournals.org)
- In order to further elucidate the molecular mechanisms of NR4A2, we conducted a gene expression screen to identify novel transcriptional targets of NR4A2 that may contribute to arthritis progression. (biomedcentral.com)
- The ultimate goal is to use this knowledge to design targeted molecular inhibitors for the treatment of cancer.Much of our work is centered on a family of cellular regulators called STATs, or signal transducers and activators of transcription. (dana-farber.org)
- Pim-1 is a molecular target of the transcription factor Hoxa9. (biomedcentral.com)
- Subsequent analysis focused on the most potently induced gene prolactin (PRL). (biomedcentral.com)
- Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. (rcsb.org)
- Mechanistically, loss of NMI had negative impacts on STAT5-driven expression of TGFβ signaling repressor, SMAD7. (biomedcentral.com)
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation and maturation of myeloid progenitor cells in vitro and in vivo. (ashpublications.org)
- PDGF is a principal survival factor that inhibits apoptosis and promotes proliferation. (bio-rad.com)
- As mediators of cytokine-induced and growth factor-induced gene expression, signal transducers and activators of transcription (STATs) are involved in cellular differentiation, proliferation, and survival. (biomedcentral.com)
- Dietary omega (n)-3, n-6 or n-9 fatty acids can variably alter (i.e. increase or decrease) the production of ILs (interleukins) and TNF (tumour necrosis factor) as well as the activity (e.g. phagocytosis) and proliferation of leukocytes (e.g. (biomedcentral.com)
- Ets1 overexpression in stratified squamous epithelial cells causes pro-oncogenic changes, such as suspension of terminal differentiation, high secretion of matrix metalloproteases (Mmps), epidermal growth factor ligands, and inflammatory mediators. (wikipedia.org)
- It is well established that milk production of the dairy cow is a function of mammary epithelial cell (MEC) number and activity and that these factors can be influenced by diverse environmental influences and management practises (nutrition, milk frequency, photoperiod, udder health, hormonal and local effectors). (springer.com)
- Here, we performed a screen to identify TME cytokines and growth factors that promote epithelial-mesenchymal plasticity, and acquisition of cancer stem cell (CSC) properties. (pubmedcentralcanada.ca)
- STAT5 activity is induced by numerous cytokines and growth factors. (merckmillipore.com)
- Of 28 TME cytokines and growth factors tested, we identified Oncostatin M (OSM) as the most potent inducer of mesenchymal/CSC properties. (pubmedcentralcanada.ca)
- STATs (signal transducers and activators of transcription) are a family of cytoplasmic latent transcription factors that are activated to regulate gene expression in response to a large number of extracellular signaling polypeptides including cytokines, interferons, and growth factors. (acris-antibodies.com)
- This postdoctoral research was involved in investigating the mechanisms by which hematopoietic cytokines can regulate gene expression through transcription factor phosphorylation. (umcutrecht.nl)
- We show that, at drug concentrations routinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expression of STAT3 target genes, and the viability of STAT3-dependent hematological cancer cells. (bloodjournal.org)
- These chemopreventive molecules that target the nuclear factor-κB pathway are a large, structurally diverse group, but this common target suggests that it is a critical pathway modulated in endothelial cells during tumor angiogenesis. (aacrjournals.org)
- increased ETS1 expression causes about 50 target genes to increase expression, including DNA repair genes MUTYH, BARD1, ERCC1 and XPA. (wikipedia.org)
- Recently developed small molecule inhibitors 79-6 and TG101348 that increases BCL6 target gene expression and decreases pSTAT6 levels, respectively, demonstrate that a combined targeting results in additive efficacy regarding their negative effect on cell viability. (oncotarget.com)
- Along with transcriptional co-activators and enhancers, STATs direct the transcription of their target genes. (nih.gov)
- In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes. (wikidoc.org)
- However activated GR can complex with these other transcription factors and prevent them from binding their target genes and hence repress the expression of genes that are normally upregulated by NF-κB or AP-1. (wikidoc.org)
- Nuclear EGFR targeted genes such as cyclin D1, iNOS, B Myb, Aurora A and COX 2, have already been reported, yet these scientific studies did not help cyclin D1 as the target gene co regulated by EGFR and various transcription fac tors following the infection of EBV, such as inside the function of EGFR and STAT3 co affecting on iNOS and STAT1 in breast cancer. (srcsignaling.com)
- Notably they used Chromatin Immunoprecipitation (ChIP) to confirm STAT5 binding to target DNA sequences (3). (promegaconnections.com)
- Inhibiting STAT3 expression or phosphorylation using antisense oligonucleotides and small-molecule inhibitors suppressed the growth of human and murine tumors in animal models [ 14 , 15 , 16 ], demonstrating that STAT3 is a potential target for cancer therapy. (mdpi.com)
- Male-specific hepatic Bcl6: growth hormone-induced block of transcription elongation in females and binding to target genes inversely coordinated with STAT5. (semanticscholar.org)
- Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. (rcsb.org)
- Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' ( BCL6 -binding site) or indirectly by repressing the transcriptional activity of transcription factors. (rcsb.org)
- leads to a epigenetic repression of selective NOTCH1 -target genes. (rcsb.org)
- Receptors containing either mutant CD domains (mCD PR) or point mutations of Ser81 (S79/81A PR) failed to upregulate STAT5 and Wnt1, key PR-target gene products that act as critical mediators of mammary stem cell expansion. (datamed.org)
- Poly(ADP-ribose)polymerase (PARP)14-a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs-is an ADP ribosyltransferase that interacts with Stat6, enhances induction of certain genes by IL-4, and is expressed in B lymphocytes. (pnas.org)
- STAT6 is a central mediator of IL‐4‐induced gene responses. (embopress.org)
- These findings identify p100 as a novel coactivator for STAT6 and suggest that p100 functions as a bridging factor between STAT6 and the basal transcription machinery. (embopress.org)
- Using a computational strategy to identify compounds opposing the gene expression signature of STAT3, we discovered atovaquone (Mepron), an antimicrobial approved by the US Food and Drug Administration, to be a potent STAT3 inhibitor. (bloodjournal.org)
- These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic β-cells. (diabetesjournals.org)
- Tyrosine phosphorylation is required for DNA- binding activity and dimerization. (merckmillipore.com)
- Phosphorylation of this tyrosine leads to phosphotyrosine-Src homology domain 2-mediated reciprocal dimerization. (biomedcentral.com)
- Serine phosphorylation is also required for maximal transcriptional activity (By similarity). (merckmillipore.com)
- Transcriptional activity and DNA association are determined by the transactivation and DNA-binding domains, respectively. (wikipedia.org)
- NRG1 stimulated YAP activity to an extent comparable to that of EGF (epidermal growth factor) or LPA (lysophosphatidic acid), known activators of YAP. (sciencemag.org)
- The transcriptional activity of PRRIII/IL-2rE is controlled by the functional interaction of Stat5, Ets-1, and Ets-2 in response to IL-2 stimulation ( 50 ). (asm.org)
- GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding . (genecards.org)
- All four inhibitors markedly reduced the binding activity of NF-AT and AP-1 for IL-2 gene transcription. (ubc.ca)
- Yet their influence on NF-κB and STAT5 binding activity for CD25 gene transcription was variable. (ubc.ca)
- LY294002 markedly reduced NF-κB binding activity, while U0126, SB203580 and LY294002 partially reduced STAT5 binding activity. (ubc.ca)
- Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients. (pubmedcentralcanada.ca)
- inhibits ZBTB17 transcriptional activity. (rcsb.org)
- Progestin-induced PR Ser81 phosphorylation mapped to CD domain-dependent binding of PR-B to MKP3, but did not require phosphatase activity. (datamed.org)
- MethoCult™ M3134 is suitable for the growth and enumeration of hematopoietic progenitor cells in colony-forming unit (CFU) assays of mouse bone marrow, spleen, peripheral blood, and fetal liver, when the appropriate growth factors and supplements are added. (stemcell.com)
- Tissue-specific, inducible expression of the IL-2Rα gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Rα gene transcription. (asm.org)
- ChIP assays demonstrated that wt, but not phospho-mutant (S79/81A), PR-B was co-recruited to a PRE-containing enhancer region of the Wnt1 gene along with MKP3, ck2 and STAT5. (datamed.org)
- The present article provides an overview of our current knowledge about the critical role of AKT and STAT5 in the pathophysiology of chronic myeloid leukemia and systemic mastocytosis and on their potential value as therapeutic targets in these neoplasms. (haematologica.org)
- In contrast, the STAT3 transcriptional targets VEGF and MCL-1 increased after LLL12 treatment. (springer.com)
- Both transcription factors are attractive targets for pharmaceutical intervention of disorders such as hypertriglyceridemia and obesity. (embopress.org)
- One of the most well characterized transcriptional targets of p53 is the p21WAF1 gene. (biomedcentral.com)
- Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5 , including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation. (rcsb.org)
- In order to investigate this, we perform biochemical analyses of T lymphocytes grown in the lab as primary cultures to characterise how low oxygen environments impact on cellular processes, such as signalling and gene expression, that control T lymphocyte function. (babraham.ac.uk)
- Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. (genecards.org)
- Collectively, these findings suggest the EGFR STAT3 axis signaling pathway following website is important in regulating cellular transcriptional and biologic properties in numerous carcinomas in response to various carcino gens such as virus infection. (srcsignaling.com)
- NK cells differ from ILC1 for their cytotoxic abilities, for a higher propension to circulate in the bloodstream and for the expression of lineage defining transcription factors (LDTFs) ( 7 - 9 ). (frontiersin.org)
- We showed that hypoxia inducible factor-1alpha (HIF-1alpha) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1alpha-induced invasive characteristics. (bvsalud.org)
- The STATs were recognized as ligand-induced transcription factors in interferon (IFN)-treated cells and then in cells and tissues exposed to many other signaling polypeptides ( 1-3 ). (sciencemag.org)
- Determining how oxygen levels impact on many aspects of transcription and epigenetic control of gene expression in T cells. (babraham.ac.uk)
- Our aim is to determine how these factors impact on how well T lymphocytes can destroy diseased cells and clear infections. (babraham.ac.uk)
- 5 , 24 , 25 In paired breast cancer core biopsies before and after chemotherapy, a higher percentage of CD24−/CD44+ CSC capable of forming tumorspheres exist following treatment, with the residual surviving cells harboring elevated CSC gene expression signatures. (pubmedcentralcanada.ca)
- Platelet-derived growth factors ( PDGF s) are members of a large family of growth factors secreted by human vascular endothelial cells and fibroblasts. (bio-rad.com)
- Leptin has also been shown to inhibit insulin secretion and preproinsulin gene expression in pancreatic β-cells ( 3 - 6 ), thereby establishing an adipoinsular feedback loop in concert with stimulatory action of insulin on leptin secretion from the adipose tissue ( 7 , 8 ). (diabetesjournals.org)
- The development of lymphoid cells from bone marrow progenitors is dictated by interplay between internal cues such as transcription factors and external signals like the cytokines Flt-3 ligand and Il-7. (diva-portal.org)
- The stimulation resulted in a reduced expression of pro-apoptotic genes and also mediated survival of primary progenitor cells in vitro. (diva-portal.org)
- Although high levels of leptin (corresponding to obesity condition) alone had no effect on Leydig cells' steroidogenic genes expression, it downregulated cAMP-dependent activations of the cholesterol transporter Star and of the rate-limiting steroidogenic enzyme Cyp11a1. (deepdyve.com)
- However, other transcription factors such as members of the SMAD and NFAT families may be involved and need further investigation to better define how leptin regulates their activities and their relevance for Leydig cells function. (deepdyve.com)
- In follicular helper CD4 (+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. (rcsb.org)
- These findings establish actin-regulated transcription in human T cells and suggest its role in viral oncogenesis. (biomedcentral.com)
- Thus, IL-4 is thought to promote lymphocyte survival through an IRS-2-dependent PI3K-Akt pathway analogous to one used by growth factor receptors. (pnas.org)
- Progesterone receptors (PRs) are critical context-dependent transcription factors required for normal uterine (PR-A) and mammary gland (PR-B) development. (datamed.org)
- After phosphorylation of the critical tyrosine residue (Tyr705), STAT3 homodimerization occurs followed by nuclear translocation and alteration of gene transcription. (springer.com)
- In contrast, AKT phosphorylation induced by insulin-like growth factor-I remained unchanged, showing selectivity of the compound. (aacrjournals.org)
- Signal transducers and activators of transcription (STATs) are mediators of cytokine and growth factor signaling. (biomedcentral.com)
- Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300. (ebi.ac.uk)
- STAT1 is known to associate with the transcription factors p48, Sp1, and p300. (acris-antibodies.com)
- Structural Basis for Recruitment of CBP/p300 by Hypoxia-inducible Factor-1 Alpha Proceedings of the National Academy of Sciences of the United States of America. (jove.com)
- Pubmed ID: 11959990 Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. (jove.com)
- Myc-Max dimers bind to hexameric DNA sequences (E-box) and activate transcription by recruiting multiple coactivators [ 1 ]. (biomedcentral.com)
- Deletion of the carboxyl-terminal transactivation domain of MGF-Stat5 results in sustained DNA binding and a dominant negative phenotype. (asm.org)
- The carboxyl-terminal transactivation domain of Stat5a, amino acids 722 to 794, can be conferred to the DNA-binding domain of the yeast transcription factor GAL4. (asm.org)
- STATs are activated through a process known as cytokine-mediated phosphorylation (2). (promegaconnections.com)
- On the other hand, stimulation with IFN-I or IFN-III leads to TYK2- and JAK1-mediated phosphorylation of STAT1 and STAT2. (frontiersin.org)
- Phosphoamino acid analysis also revealed that Stat5a/b phosphotyrosine levels were maximized within 1-5 min of IL2 stimulation, whereas serine phosphorylation kinetics were slower. (unimi.it)
- HDAC3-deficient macrophages possessed decreased ability to activate inflammatory gene expression in response to LPS stimulation [ 13 ]. (hindawi.com)
- After phosphorylation, STAT1 and STAT2 form heterodimers that function as more potent inducers of transcription than the STAT1 homodimer. (acris-antibodies.com)
- The later suggests that several other transcription factors may facilitate Ets1 binding to unfavorable DNA sequences. (wikipedia.org)
- Thus, 9AA treatment was highly efficient at reactivating the p53 - p21WAF1 pathway and consequently inhibiting HIV replication and transcription. (biomedcentral.com)
- This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. (cancerindex.org)
- MGF consists of 734 amino acids and has sequence homology with the 113 (Stat113) and 91 kDa (Stat91) components of ISGF3, transcription factors which are signal transducers of IFN-alpha/beta and IFN-gamma. (nih.gov)