Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
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.
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.
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.
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.
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.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
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.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
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).
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.
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.
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).
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.
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)
A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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.
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.
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.
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.
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.
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.
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.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
A 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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
A 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.
An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.
A specificity protein transcription factor that regulates expression of a variety of genes including VASCULAR ENDOTHELIAL GROWTH FACTOR and CYCLIN-DEPENDENT KINASE INHIBITOR P27.
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
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.
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.
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.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
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.
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.
Nucleic acid sequences involved in regulating the expression of genes.
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
A cell line derived from cultured tumor cells.
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.
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.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.
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.
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.
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.
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.
An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
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.
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.
A family of transcription factors that contain two ZINC FINGER MOTIFS and bind to the DNA sequence (A/T)GATA(A/G).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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)
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.
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.
A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and regulates vascular smooth muscle CELL DIFFERENTIATION.
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.
An activating transcription factor that regulates expression of a variety of genes including C-JUN GENES and TRANSFORMING GROWTH FACTOR BETA2.
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.
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.
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.
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.
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.
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.
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.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins prepared by recombinant DNA technology.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
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).
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.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
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.
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.
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.
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.
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.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
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.
Proteins found in any species of fungus.
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.
Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.
A ubiquitously expressed octamer transcription factor that regulates GENETIC TRANSCRIPTION of SMALL NUCLEAR RNA; IMMUNOGLOBULIN GENES; and HISTONE H2B genes.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
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.
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.
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.
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.
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.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.
Deletion of sequences of nucleic acids from the genetic material of an individual.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Factors that bind to RNA POLYMERASE III and aid in transcription. They include the assembly factors TFIIIA and TFIIIC and the initiation factor TFIIIB. All combine to form a preinitiation complex at the promotor that directs the binding of RNA POLYMERASE III.
A heterotetrameric transcription factor composed of two distinct proteins. Its name refers to the fact it binds to DNA sequences rich in GUANINE and ADENINE. GA-binding protein integrates a variety of SIGNAL TRANSDUCTION PATHWAYS and regulates expression of GENES involved in CELL CYCLE control, PROTEIN BIOSYNTHESIS, and cellular METABOLISM.
Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.
An early growth response transcription factor that has been implicated in regulation of CELL PROLIFERATION and APOPTOSIS.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
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).)
Transport proteins that carry specific substances in the blood or across cell membranes.
A family of low-molecular weight, non-histone proteins found in chromatin.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Proteins found in any species of bacterium.
An ets proto-oncogene expressed primarily in adult LYMPHOID TISSUE; BRAIN; and VASCULAR ENDOTHELIAL CELLS.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.
A transcription factor that takes part in WNT signaling pathway. The activity of the protein is regulated via its interaction with BETA CATENIN. Transcription factor 7-like 2 protein plays an important role in the embryogenesis of the PANCREAS and ISLET CELLS.
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.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
A basic helix-loop-helix transcription factor that was originally identified in DROSOPHILA as essential for proper gastrulation and MESODERM formation. It plays an important role in EMBRYONIC DEVELOPMENT and CELL DIFFERENTIATION of MUSCLE CELLS, and is found in a wide variety of organisms.
The biosynthesis of DNA carried out on a template of RNA.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
A species of 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.
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.
Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
Formation of an acetyl derivative. (Stedman, 25th ed)
A tissue-specific subunit of NF-E2 transcription factor that interacts with small MAF PROTEINS to regulate gene expression. P45 NF-E2 protein is expressed primarily in MEGAKARYOCYTES; ERYTHROID CELLS; and MAST CELLS.
Elements of limited time intervals, contributing to particular results or situations.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
One of several general transcription factors that are specific for RNA POLYMERASE III. TFIIIB recruits and positions pol III over the initiation site and remains stably bound to the DNA through multiple rounds of re-initiation by RNA POLYMERASE III.
One of the BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS that is synthesized as a membrane-bound protein in the ENDOPLASMIC RETICULUM. In response to endoplasmic reticulum stress it translocates to the GOLGI APPARATUS. It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the unfolded protein response.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A family of mammalian POU domain factors that are expressed predominately in NEURONS.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A subclass of SOX transcription factors that are expressed in neuronal tissue where they may play a role in the regulation of CELL DIFFERENTIATION. Members of this subclass are generally considered to be transcriptional activators.
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.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
A basic-leucine zipper transcription factor that regulates GLOBIN gene expression and is related to TRANSCRIPTION FACTOR AP-1. NF-E2 consists of a small MAF protein subunit and a tissue-restricted 45 kDa subunit.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
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.
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A heterotrimeric DNA-binding protein that binds to CCAAT motifs in the promoters of eukaryotic genes. It is composed of three subunits: A, B and C.
A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.
Ubiquitously expressed basic HELIX-LOOP-HELIX MOTIF transcription factors. They bind CANNTG sequences in the promoters of a variety of GENES involved in carbohydrate and lipid metabolism.
A subclass of closely-related SOX transcription factors. Members of this subfamily have been implicated in regulating the differentiation of OLIGODENDROCYTES during neural crest formation and in CHONDROGENESIS.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.

The significance of tetramerization in promoter recruitment by Stat5. (1/1703)

Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Ralpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential.  (+info)

Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis. (2/1703)

Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Galphai as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.  (+info)

Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1alpha. (3/1703)

Salmon insulin-like growth factor-I (sIGF-I) expression is, as in mammals, induced by growth hormone (GH). To elucidate the mechanism by which GH stimulates the transcription of the IGF-I gene, we transiently transfected Hep3B cells expressing the rat GH receptor with a sIGF-I promoter-luciferase reporter construct. Activation of the construct by GH added to the medium of the transfected cells was observed when two specific transcription factors, STAT5 and HNF-1alpha, were simultaneously overexpressed in these cells. This finding demonstrates for the first time a GH-dependent activation of an IGF-I promoter construct in an immortalized laboratory cell line.  (+info)

Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells. (4/1703)

The type I human T-cell leukemia virus (HTLV-I) induces abnormal growth and subsequent transformation of T cells, which is associated with the development of an acute T-cell malignancy termed adult T-cell leukemia. A characteristic of HTLV-I-transformed T cells is the constitutive nuclear expression of NF-kappaB/Rel family of transcription factors, which appears to be essential for the growth of these transformed cells. Although NF-kappaB/Rel factors are known to induce the expression of T-cell growth factor interleukin (IL)-2, it is unclear how they participate in the IL-2-independent growth of HTLV-I-transformed cells. In this study, we show that certain NF-kappaB/Rel members, predominantly c-Rel, interact with enhancer sequences for STAT5, a key transcription factor mediating IL-2-induced T-cell proliferation. Reporter gene assays reveal that the binding of c-Rel to the STAT5 site present in the Fc gammaR1 gene leads to potent transactivation of this enhancer. Binding of c-Rel to the Fc gammaR1 STAT site also occurs in human peripheral blood T cells immortalized with HTLV-I in vitro and is correlated with enhanced levels of proliferation of these cells. These results raise the possibility that NF-kappaB/Rel may participate in the growth control of HTLV-I-transformed T cells by regulating genes driven by both kappaB and certain STAT enhancers.  (+info)

Thrombopoietin-induced conformational change in p53 lies downstream of the p44/p42 mitogen activated protein kinase cascade in the human growth factor-dependent cell line M07e. (5/1703)

Thrombopoietin is a cytokine with potent megakaryocytopoietic and thrombopoietic activities in vivo. Wild-type p53 is a conformationally flexible, anti-oncogenic transcription factor that plays a principal role in mediating growth factor withdrawal-induced apoptosis in factor-dependent hematopoietic cells. We recently reported that Tpo induces a conformational change in and functional inactivation of p53, coincident with its anti-apoptotic effects, in the human factor-dependent cell line M07e. In an effort to identify potential signaling cascades through which Tpo illicits these effects on p53, we report here that treating M07e cells with MAPK kinase inhibitor PD98059 dramatically suppressed Tpo-induced conformational change in p53 as well as Tpo-enhanced viability in M07e cells in a p53-dependent manner. Furthermore, the expression of constitutively active Raf1 in M07e cells induced conformational change in p53 independent of Tpo stimulation. Inhibition of the JAK/STAT pathway revealed that JAK/STAT signaling plays an insignificant role in conformational modulation of p53 and apoptosis suppression. Inhibition of phosphatidylinositol-3 kinase did not have a significant effect on p53 conformation but did have a weak but significant effect on Tpo-enhanced viability. Cytokine-induced activation of the MAPK pathway and the subsequent functional neutralization of p53, may be an event by which apoptosis is commonly suppressed in hematopoiesis.  (+info)

Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells. (6/1703)

STAT5 is a member of a family of transcription factors that participate in the signal transduction pathways of many hormones and cytokines. Although STAT5 is suggested to play a crucial role in the biological effects of cytokines, its downstream target(s) associated with cell growth control is largely unknown. In a human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-rasG12V) enabled F-36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6-STAT5A and H-rasG12V individually and cooperatively transactivated the cyclin D1 promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced cyclin D1 promoter activities in F-36P-mpl cells. Using a series of mutant cyclin D1 promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter through the potential STAT-binding sequence at -481 bp. In electrophoretic mobility shift assays, STAT5 bound to the element in response to IL-3. Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was restored by expression of cyclin D1. Thus STAT5, in addition to ras signaling, appears to mediate transcriptional regulation of cyclin D1, thereby contributing to cytokine-dependent growth of hematopoietic cells.  (+info)

Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene expression. Impact of STAT5a gene disruption. (7/1703)

Stat5b gene disruption leads to an apparent growth hormone (GH) pulse insensitivity associated with loss of male-characteristic body growth rates and male-specific liver gene expression (Udy, G. B., Towers, R. P., Snell, R. G., Wilkins, R. J., Park, S. H., Ram, P. A., Waxman, D. J., and Davey, H. W. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 7239-7244). In the present study, disruption of the mouse Stat5a gene, whose coding sequence is approximately 90% identical to the Stat5b gene, resulted in no loss of expression in male mice of several sex-dependent, GH-regulated liver cytochrome P450 (CYP) enzymes. By contrast, the loss of STAT5b feminized the livers of males by decreasing expression of male-specific CYPs (CYP2D9 and testosterone 16alpha-hydroxylase) while increasing to female levels several female-predominant liver CYPs (CYP3A, CYP2B, and testosterone 6beta-hydroxylase). Since STAT5a is thus nonessential for these male GH responses, STAT5b homodimers, but not STAT5a-STAT5b heterodimers, probably mediate the sexually dimorphic effects of male GH pulses on liver CYP expression. In female mice, however, disruption of either Stat5a or Stat5b led to striking decreases in several liver CYP-catalyzed testosterone hydroxylase activities. Stat5a or Stat5b gene disruption also led to the loss of a female-specific, GH-regulated hepatic CYP2B enzyme. STAT5a, which is much less abundant in liver than STAT5b, and STAT5b are therefore both required for constitutive expression in female but not male mouse liver of certain GH-regulated CYP steroid hydroxylases, suggesting that STAT5 protein heterodimerization is an important determinant of the sex-dependent and gene-specific effects that GH has on the liver.  (+info)

Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells. (8/1703)

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that has antiviral, antiproliferative, and immunoregulatory functions. There is increasing evidence that IFN-alpha has an important role in T-cell biology. We have analyzed the expression of IL-2Ralpha, c-myc, and pim-1 genes in anti-CD3-activated human T lymphocytes. The induction of these genes is associated with interleukin-2 (IL-2)-induced T-cell proliferation. Treatment of T lymphocytes with IFN-alpha, IL-2, IL-12, and IL-15 upregulated IL-2Ralpha, c-myc, and pim-1 gene expression. IFN-alpha also sensitized T cells to IL-2-induced proliferation, further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis. When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha, pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN-alpha-induced binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements. Yet, IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site. IFN-alpha enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a, and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements. Taken together, our results suggest that IFN-alpha, IL-2, IL-12, and IL-15 have overlapping activities on human T cells. These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine.  (+info)

Although the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a
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Product Information: Product namePhospho-Stat3-Y705 pAbIsotypeIgGFormLyophilized or LiquidTested applicationsWB,IHC,IF,ELISASpecies reactivityHuman,Mouse,RatHost SpeciesRabbitPurityAffinity purif
SI}} {{CMG}} ==Overview== [[Image:Stat domain structure.png,thumb,350px,left,Domains and covalent modification sites of STAT proteins.]] The Signal Transducers and Activator of Transcription (STAT) proteins regulate many aspects of [[cell growth]], survival and [[differentiation]]. The [[transcription factor]]s of this family are activated by the Janus Kinase [[JAK]] and dysregulation of this pathway is frequently observed in primary tumors and leads to increased [[angiogenesis]], enhanced survival of [[tumors]] and [[immunosuppression]]. [[Knockout]] studies have provided evidence that STAT proteins are involved in the development and function of the [[immune system]] and play a role in maintaining [[immune tolerance]] and tumor surveillance. ==STAT family== The first two STAT proteins were identified in the interferon system The seven mammalian STAT family members identified are: [[STAT1]], [[STAT2]], [[STAT3]], [[STAT4]], [[STAT5]] a and b, and [[STAT6]]. STAT1 homodimers are involved ...
Activity:. STAT5-IN-1 is a STAT5 inhibitor with an IC50 of 47 μM for STAT5β isoform. IC50 & Target: IC50: 47 μM (STAT5β)[1] In Vitro: The signal transducer and activator of transcription 5 (STAT5) is a member of the STAT family of proteins, implicated in cell growth and differentiation. STAT5-IN-1 inhibits STAT5 by binding to the SH2 domain. The functions of the SH2 domains of STAT3, STAT1, and of the tyrosine kinase Lck are inhibited to a lesser extent (IC50>500 µM). STAT5-IN-1 block STAT5/STAT5 DNA binding in K562 nuclear extracts. Substitution of the hydrogen at C6 of the chromone ring by an ethyl group does not affect activity of STAT5-IN-1 against STAT5β, but leads to complete loss of selectivity against other STAT family members[1]. Protocol:. References:. ...
Abstract: : Purpose: STAT proteins are a family of transcription factors that mediate the action of several growth factors. The purpose of this study was to assess the effect of PDGF in STAT1 and STAT3 synthesis. Methods: Primary hRPE cell cultures were established from four human eyes obtained from the Michigan Eye Bank. Cells were allowed to grow to confluence and treated with PDGF and genistein. Cell viability was determined by the trypan blue exclusion method. Cell proliferation was monitored by 3H-thymidine (3H-thy) incorporation. 14C-methionine labeled-intracellular STAT1 and STAT3 synthesis was determined by immunoprecipitation using STAT1 and STAT3 antibodies and SDS-PAGE analysis. Data were analyzed by Student t test and Wilcoxon Signed Rank test. P,0.05 was considered to be significantly different. Results: PDGF increased hRPE cell number and 3H-thymidine incorporation in a dose dependent manner. PDGF also increased 14C-methionine STAT 1 and STAT 3 protein synthesis in a dose ...
Purified Recombinant Human STAT3 Protein, Myc/DDK-tagged, C13 and N15-labeled from Creative Biomart. Recombinant Human STAT3 Protein, Myc/DDK-tagged, C13 and N15-labeled can be used for research.
The activation of Stat5 proteins (Stat5a and Stat5b) is one of the earliest signaling events mediated by IL-2 family cytokines, allowing the rapid delivery of signals from the membrane to the nucleus. Among STAT family proteins, Stat5a and Stat5b are the two most closely related STAT proteins. Toget …
MW 365.36, Purity | 97%. Selective STAT3 inhibitor (IC50 values are 86, 160, 166 and |300 μM for STAT3.STAT3, STAT1.STAT3 STAT1.STAT1 and STAT5.STAT5 DNA binding activity respectively). Suppresses…
One subunit of the interleukin-6 (IL-6) receptor, which activates Janus kinases upon ligand binding, is gp130. Tyrosine phosphorylation of gp130 recruits protein phosphatase 2 (SHP2) and signal transducer and activator 3 (STAT3). Ohtani et al. utilized knock-in technology to create mice deficient in only the gp130-mediated SHP2 pathway or the gp130-mediated STAT3 pathway to dissect the roles these two pathways play in IL-6 signaling. Eliminating the SHP2 response resulted in prolonged IL-6-induced STAT3 phosphorylation. STAT3 signaling was required for embryonic development, where as SHP2 signaling-deficient mice were viable and fertile. STAT3 signaling was required for induction of astrocytes by IL-6 cytokines. Reciprocal roles for STAT3 signaling and SHP2 signaling (STAT3 providing a positive signal and SHP2 providing a negative signal) were found for cytokine and immunoglobulin responses and lymphoid organ homeostasis. Thus, mice deficient in SHP2 signaling developed splenomegaly and ...
Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN), which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and
This study showed that gp130, a member of the cytokine receptor superfamily, efficiently activates the TAK1 through the YXXQ motif in gp130, and this kinase preferentially activates the downstream kinase NLK, which is responsible for STAT3 Ser-727 phosphorylation via the YXXQ motif-derived signal. Furthermore, this study revealed a novel role for STAT3 in IL-6-induced NLK activation but not in TGFβ-induced NLK activation. STAT3 functions as a scaffold for TAK1 and NLK specifically in IL-6 signaling by binding them at its carboxyl-terminal region. The following observations support the idea that this interaction is physiologically significant: (i) most TAK1-NLK interactions in the nuclear extracts of IL-6-stimulated HepG2 cells depended on the presence of STAT3 (Fig. 5B ); (ii) the IL-6-induced NLK activation was greatly decreased in HepG2-STAT3KD cells; (iii) STAT3 and TAK1 were independently activated by IL-6, even at low concentrations, and they then translocated into the nucleus (Figs. 4B ...
View Notes - Stat841f09 - Wiki Course Notes from STAT 441/8 stat 441/8 at University of Waterloo, Waterloo. 10/09/2013 Stat841 - Wiki Cour se Notes Stat841 From Wiki Cours e Notes Contents 1
кДНК STAT3 была впервые клонирована в 1994 году под именем APRF (англ. acute-phase response factor)[2]. В 1996 году была открыта укороченная изоформа мРНК STAT3, которая образуется в результате альтернативного сплайсинга. В этой мРНК отсутствует фрагмент длиной около 50 нуклеотидов, соответствующая изоформа белка называется STAT3β и является негативным регулятором транскрипции[3].. Полноразмерный белок STAT3α состоит из 770 аминокислотных остатков и имеет молекулярную массу около 92 кДа. Изоформа STAT3β имеет молекулярную массу около 80 кДа[4].. STAT3 имеет типичную для всех STAT-белков ...
Recombinant Human STAT1 protein Full length protein datasheet (ab82610). Abcam offers quality products including antibodies, assays and other reagents.
References for Abcams Recombinant human STAT2 protein (ab81880). Please let us know if you have used this product in your publication
STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 …
Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as undruggable. We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving ...
STAT6 is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by…
siRNA mediated knockdown of STAT3. A. Histogram of STAT3 levels in SW480 colon carcinoma cells treated with STAT3 and NTC (non-targeting) siRNAs. Red bars denot
Pub. L. 92-573, 86 Stat. 1207 (15 U.S.C. 2051-81) as amended by Pub. L. 94-284, 90 Stat. 503, Pub. L. 95-319, 92 Stat. 386, Pub. L. 95-631, 92 Stat. 3742; Pub. L. 90-189, 81 Stat. 568 (15 U.S.C. 1191-1204); Pub. L. 86-613, 74 Stat. 372, as amended by Pub. L. 89-756, 80 Stat. 1303, and Pub. L. 91-113, 83 Stat. 187 (15 U.S.C. 1261-74); Pub. L. 91-601, 84 Stat. 1670 (15 U.S.C. 1471-76) and the Act of Aug. 7, 1956, 70 Stat. 953 (15 U.S.C. 1211-14 ...
Complete information for STAT2 gene (Protein Coding), Signal Transducer And Activator Of Transcription 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The Ac2-26-mediated STAT3 activation is JAK-dependent and induces nuclear translocation and DNA binding of phosphorylated STAT3 as well as increased SOCS3 expre
Commander STAT3 kit ELISA pour beaucoup de réactivité. Poulet, Boeuf (Vache), Chien et plus. Comparez STAT3 kit ELISA et trouvez le bon produit chez anticorps-enligne.fr.
View Notes - lecture14 from STAT 302 at UBC. Stat 302, Introduction to Probability Jiahua Chen January-April 2011 Jiahua Chen () Lecture 14 January-April 2011 1 / 26 Variance formula, again Let X and
View mouse Stat6 Chr10:127642986-127660957 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
library(ggpubr) p ,- ggboxplot(ToothGrowth, x = supp, y = len, color = supp, palette = jco, add = jitter) p + stat_compare_means( aes(label = format.pval(..p.adj.., digits = 3)), label.x = 1.5, label.y = 40) ...
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STAT3兔单克隆抗体[E121-21](ab32500)可与人样本反应并经WB, IP, IHC实验严格验证,被6篇文献引用并得到3个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
L to pomalu kon , dovolenou m me za sebou a u n m j p ipom naj jen fotografie. Ale mo n tak sexy op len k e. Kdo z n s by necht l zastavit as a z stat t hl , odpo at a do bronzova.
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Since remdesivir became the first medicine shown to have an impact on Covid-19, the big question has been what Gilead would charge for the drug.
Since remdesivir became the first medicine shown to have an impact on Covid-19, the big question has been what Gilead would charge for the drug.
Subjects: Statistics Theory (math.ST); Optimization and Control (math.OC); Probability (math.PR); Computation (stat.CO); Methodology (stat.ME ...
We recently determined that erythropoietin (EPO) activates 3 members of the signal transducer and activator of transcription (STAT) family, Stat1α, Stat3, and Stat5, in the human EPO-dependent cell lines, UT-7 and UT-7/EPO (Kirito et al, J Biol Chem 272:16507, 1997). In addition, we have shown that Stat1α, but not Stat3, is involved in EPO-induced cellular proliferation. In this study, we examined the roles of Stat1α and Stat3 in EPO-induced erythroid differentiation. UT-7/GM was used as a model system, because this cell line can differentiate into erythroid-lineage cells with EPO treatment (Komatsu et al, Blood 89:4021, 1997). We found that EPO did not activate Stat1α or Stat3 in UT-7/GM cells. Transfection experiments showed that both Stat1α and Stat3 inhibited the induction by EPO of γ-globin and erythroid-specific 5-aminolevulinate synthetase transcripts, resulting in a reduction of the percentage of hemoglobin-positive cells. Dominant negative forms of Stat1α or Stat3 promoted the ...
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the STAT3 gene. It is a member of the STAT protein family. STAT3 is a member of the STAT protein family. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), form homo- or heterodimers, and translocate to the cell nucleus where they act as transcription activators. Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons, epidermal growth factor (EGF), Interleukin (IL-)5 and IL-6. Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by Mitogen-activated protein kinases (MAPK) and through c-src non-receptor tyrosine kinase. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. STAT3-deficient mouse embryos cannot develop ...
Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells. These processes are associated with STAT1-dependent gene expression and an interaction between endogenous STAT? and ACK1. Moreover, the E3 ubiquitin ligase seven-in-absentia homolog-2 (SIAH2), which targets ACK1 through valine-909 for proteasomal degradation, attenuates the ACK1-STAT1 signalling node. We further show that ACK1 promotes the phosphorylation and nuclear accumulation of STAT3 in cultured cells and that the levels of ACK1 correlate positively with the levels of tyrosine phosphorylated STAT3 in primary lung adenocarcinoma (ADC) cells. Global analysis of ACK1 interaction partners validated the ...
Background: The transcription factor Signal Transducer and Activator of Transcription Factor 3 (STAT3) is implicated in acquired drug resistance, metastases and immune suppression in prostate cancer and is a potential target in drug-resistant prostate cancer. Today, the treatment options for metastatic drug-resistant prostate cancer are very limited and existing immunotherapies have so far shown low efficacy. Cancer cells may avoid immune responses by expressing immunosuppressive markers or activating immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) play a major role in the suppression of antitumor immunity and active STAT3 signaling has been shown to be involved in the immunosuppressive functions of these cells. Elevated levels of MDSC have been found in the peripheral blood and at the tumor site of prostate cancer patients and to correlate with disease progression.. Aims: In this study we aimed to investigate if human monocytes could be induced to differentiate into ...
Serous papillary endometrial cancers (SPEC) are highly progressive with poor prognosis, and its oncogenic profile is known different from endometrioid endometrial cancers. It, however, still remains unclear that which pathway promotes tumor progression. The IFN-γ transcription factor signal transducer and activator of transcription 1 (STAT1) has been considered as a tumor suppressor with transcription-dependent and transcription-independent mechanisms, but recent studies showed STAT1 was associated with poor prognosis in some cancers with unclear mechanisms.. In this study, we performed a genome-wide analysis by microarray analysis of 63 human endometrial cancers which revealed STAT1 pathway was constitutively up-regulated in SPEC, and its expression was confirmed significantly higher in SPECs tissue cancer by immunohistochemical staining (p,0.001). Immunohistochemical staining also exhibited co-localization of ICAM-1 and PD-L1 at tumor frontier with CD8-T cells (p,0.001) as well as STAT1 ...
STAT proteins ( called Signal Transducers and Activators of Transcription ) are a group of proteins involved in the transmission of information from the cell surface to the nucleus and activate gene transcription . They are activated in response to a number of cytokines , growth factors and hormones. Until now identified six STAT proteins : STAT1 , 2, 3 , 4, 5a/5b , 6 So far it was found that they play an important role in many physiopathological processes , starting from the immune responses, cell cycle regulation and malignant transformation of cells. There are also reports that alterations in signaling through the JAK- STAT in some diseases of the hematopoietic system . The paper discusses the structure, functioning and methods of inactivation of STAT proteins . Moreover presents the latest information on the role of STAT5 proteins in the functioning of the hematopoietic system , immune , and his participation in the process of carcinogenesis .. ...
An article published in the October 25, 2011 edition of PNAS explored the study of Dr. Francesa Zammarchi et al on the alternative splicing that leads to two isoforms of STAT3: STAT3α and STAT3β. Exon 23, which includes the two amino acid residues necessary for activation of the STAT3 TF, can be fully or partially included in the final product. If the entire exon is included, STAT3α is formed and the protein is fully functional. If the 55 amino acids at the end of exon 23 are excluded from the final product, then STAT3β is made. The premature termination of the protein causes serine 727, a necessary residue for phosphorylation and activation of the STAT3 protein, to be truncated. This renders STAT3β able to maintain its DNA binding function, but not able to be fully active as a transcription factor ...
Signal transducer and activator of transcription 5 (Stat5) belongs to a family of cytoplasmic transcription factors that can be activated (phosphorylated) by a cell surface receptor. Phosphorylation at Tyr694 is obligatory for Stat5 activation. Stat5 has two isoforms, Stat5 alpha and Stat5 beta. Aberrant Stat5 activation has been implicated in the pathogenesis of chronic myelogenous leukemia, prostate and breast cancer and tumor metastasis. Stat5 is localized in the cytoplasm and upon phosphorylation at Y694 is translocated to the nucleus. Ideal for Cancer, Chromatin & Nuclear Signaling and Signal Transduction research.
The transcription factor STAT3 has multiple functions in fertility, embryonal development, the acute-phase response of the liver and the regulation of immune responses (Levy and Lee, 2002). Only recently, the importance of dysregulated STAT3 activation for the progression of cancer has been fully recognized (Darnell, 2005; Yu and Jove, 2004). STAT3 not only acts cell-autonomously by stimulating cell proliferation and preventing apoptosis but also facilitates immune evasion of tumor cells (Wang et al., 2004). STAT3 promotes tumor angiogenesis through the induction of VEGF (Niu et al., 2002) and by acting downstream of the VEGF receptor (Yahata et al., 2003). Furthermore, a function of STAT3 in tumor invasion and metastasis by upregulation of matrix metalloproteinases has been established (Itoh et al., 2005). STAT3 consists of an N-terminal multimerization domain, followed by a coiled-coil domain, the DNA-binding domain, a single SH2 domain and finally the transactivation domain (TAD). The ...
In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10(-6) M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.
The standard techniques of multiple regression analysis, analysis of variance, and analysis of covariance, and their role in observational and experimental studies. This course may not be used to satisfy the upper division requirements of the Statistics major or honours program. Prerequisite: One of STAT 201, STAT 203, STAT 205, STAT 270, or BUEC 232. Quantitative. ...
Stats, sometimes called Ability Scores, are numbers used to represent a characters strengths and weaknesses along a spectrum.. In Dungeons & Dragons, the classic six stats are Strength, Dexterity, Constitution, Intelligence, Wisdom and Charisma.. Stats are often used in connection with Risk Resolution, such as with a d20 Over Stat or a d20 Under Stat.. Stats can be improved by increasing a characters Experience Points, either by increasing in level or via an XP purchase system.. The initial values for each tend to be set by rolling dice, Point Buy or Stat Array.. In some systems, stats absorb harm via [[Stat_Reduction?]]. ...
STAT5-Interacting Proteins: A Synopsis of Proteins that Regulate STAT5 Activity. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
S A S S A M P L E L I B R A R Y */ /* */ /* NAME: PHRCRSK */ /* TITLE: Regression Analysis for Competing-Risks Data */ /* PRODUCT: STAT */ /* SYSTEM: ALL */ /* KEYS: Competing Risks, Cause-Specific Hazard, Sub- */ /* distribution Hazard */ /* PROCS: PHREG */ /* DATA: Pintilie, M. (2006): Competing Risks -- A Practical */ /* Perspective */ /* SUPPORT: sasycs */ /* MISC: */ /****************************************************************/ proc format; value $ node N = 0 E= 0 Y = 1; data hypoxia; input pelvicln $ pelrec$ disrec $ tumsize hgb ifp age hp5 survtime stat dftime dfcens resp $ stnum; if pelrec=Y then cens=1; else if disrec=Y then cens=2; else cens=0; if disrec=Y then cens2=1; else if pelrec=Y then cens2=2; else cens2=0; format pelvicln $node.; datalines; N N N 7.0 119 8.0 78 32.1428571 6.152 0 6.152 0 CR 1 N N N 2.0 131 8.2 69 2.1739130 8.008 0 8.008 0 CR 2 N Y N 10.0 126 8.6 55 52.3255814 0.621 1 0.003 1 NR 3 N Y Y 8.0 141 3.3 55 3.2608696 1.120 1 1.073 1 CR 4 Y Y N 8.0 ...
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These results suggest that morusin could be a potentially therapeutic agent for prostate cancer by reducing STAT3 activity and inducing apoptosis.
Enrollment and Prerequisites. This is a course in applied statistics, using numerous examples, rather than a course in mathematical statistics; but it is NOT an introductory first course in either statistical modelling or basic statistics. We assume you have already completed a course such as STAT2008 Regression Modelling as an essential prerequisite AND that you have also. completed the equivalent of an introductory course in basic statistics (such as STAT1003 or STAT1008) that is an essential prerequisite to the STAT2008 course.. The course also uses the R statistical package, which applies matrix algebra to implement the linear modelling techniques. An understanding of matrix algebra (equivalent to an. introductory mathematics course such as MATH1113) would be helpful in understanding how the R routines work, but such knowledge is not a required prerequisite nor an. examinable part of this course.. Scaling. If moderation of marks is required, then marks may be scaled. Your final mark for the ...
优异的STAT3兔单抗(ab76315)经WB, IP, IHC-P, ICC实验严格验证,可用于小鼠, 大鼠和人。被多篇文献引用并有多个独立的用户反馈。中国75%以上现货。
from sklearn.metrics import mean_squared_error #均方误差 from sklearn.metrics import mean_absolute_error #平方绝对误差 from sklearn.metrics import r2_score#R square #调用 mean_squared_error(y_test,y_predict) mean_absolute_error(y_test,y_predict) r2_score(y_test,y_predict ...
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[quote:84c7=kingraf]Andy is going through a mid-career crisis. Baby. wife. Chucking balls at umpires. Mild accusations of fellow players doping. Champion of w
I spend my time studying, exercising, eating and travelling - not always in that order!! Sporadically updated (usually when Im busy procrastinating ...
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When Ets1 interacts with other transcription factors (Runx1, Pax5, TFE3, and USF1) its final effect on transcription depends on ... AP1, STAT5 and VDR bind to C-terminal domain. Also, ETS1 has been shown to interact with TTRAP, UBE2I and Death associated ... epidermal growth factor ligands, and inflammatory mediators. Ets1 directly interacts with various transcription factors. Their ... The protein encoded by this gene belongs to the ETS family of transcription factors. There are 28 ETS genes in humans and 27 in ...
Nemetz C, Hocke GM (March 1998). "Transcription factor Stat5 is an early marker of differentiation of murine embryonic stem ... 2005). "Leukemia inhibitory factor as an anti-apoptotic mitogen for pluripotent mouse embryonic stem cells in a serum-free ... Lane MA, Chen AC, Roman SD, Derguini F, Gudas LJ (November 1999). "Removal of LIF (leukemia inhibitory factor) results in ... March 1997). "Factors predicting morbidity following hematopoietic stem cell transplantation". Bone Marrow Transplantation. 19 ...
This is because STRA6 signaling results in activation of transcription factor STAT5 target genes. One of these target genes is ... resulting in the activation of transcription factor, STAT5. These two functions-retinol transporter and cytokine receptor-while ... This phosphorylation activates STAT5 which then makes its way to the nucleus to induce expression of target genes including ... Following the release of holo-CRBP-I from intercellular STRA6, STAT5 is recruited to STRA6 phosphorylated Y643 region where it ...
After binding STAT5 phosphorylation is induced, resulting in the expression of upstream transcription factors. TSLP expression ... The factors inducing the activation of TSLP release are not clearly defined. Expression of TSLP is enhanced under asthma-like ... Isaksen DE, Baumann H, Trobridge PA, Farr AG, Levin SD, Ziegler SF (December 1999). "Requirement for stat5 in thymic stromal ... The TH2 cells then release factors promoting an inflammatory reaction following the repeated contact with a specific antigen in ...
IL-3/Receptor complex induces JAK2/STAT5 cell signalization pathway. It can stimulate transcription factor c‑myc (activation of ... Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the ... It has been shown that combination of IL-3, GM-CSF and stem cell factor enhances peripheral blood stem cells during high-dose ... IL-3 shares the β subunit with IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). This β subunit sharing ...
EpoR induced Jak2-Stat5 signaling, together with transcriptional factor GATA-1, induces the transcription of pro-survival ... "Activation of the erythropoietin receptor promoter by transcription factor GATA-1". Proceedings of the National Academy of ... phosphatidylinositol 3-kinase/AKT pathway and STAT transcription factors, phosphotyrosines also serve as docking sites for ... Chin H, Nakamura N, Kamiyama R, Miyasaka N, Ihle JN, Miura O (Dec 1996). "Physical and functional interactions between Stat5 ...
STAT5, and STAT6 transcription factors are activated to elicit downstream signaling events. IL-15 and its receptor subunit ... Phosphorylation STATs form transcription factors and activate transcription of appropriate genes. The β chain of IL-15R ... It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of transcription factors ... which leads to phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3) and STAT5. Due to ...
This phosphorylation recruits STAT transcription factors, predominantly STAT5, which dimerize and migrate to the cell nucleus ... PLC activates 3 major transcription factors and their pathways: NFAT, NFkB and AP-1. After costimulation from CD28 the optimal ... It cooperates with other transcription factors including NFkB and Oct. NFkB is translocated to the nucleus after costimulation ... The key factor was isolated from cultured mouse cells in 1979 and from cultured human cells in 1980. The gene for human IL-2 ...
"IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in ... Pastorcic M, Das HK (Nov 2000). "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and ... The protein encoded by this gene belongs to the ETS family of transcription factors. ETS2 has been shown to interact with: C- ... Basuyaux JP, Ferreira E, Stéhelin D, Butticè G (Oct 1997). "The Ets transcription factors interact with each other and with the ...
These signaling pathways lead to activation of many transcription factors, such as NF-κB, AP-1, c-Jun N-terminal kinase (JNK) ... IL-33 in combination with some STAT5 activators, such as IL-2, IL-7 or TSLP, up-regulates expression of its own receptor on ... Its expression is induced by transcription factor NF-κB after exposure of innate immune cells to alarmins. This occurs, for ... This up-regulation is directly controlled by GATA3 transcription factor. IL-33 combined with IL-2, IL-7 or TSLP also stimulates ...
... because the receptors for these growth factors require JAK2 for signal transduction. An inhibitor of JAK2-STAT5, AZD1480, was ... "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". The Journal of Biological ... and on the RUSH transcription factors. Janus kinase inhibitor, medical drugs under development Ruxolitinib GRCh38: Ensembl ... Barahmand-Pour F, Meinke A, Groner B, Decker T (May 1998). "Jak2-Stat5 interactions analyzed in yeast". The Journal of ...
STAT5, downstream factor of IL-2, induce TH9 cells IL-9. STAT5 directly bind to Il-9 gene promoter, although it has not yet ... STAT6 repress the expression of transcription factors T-bet and Foxp3 in TH9 cells, that normally block IL-9 production. GATA-3 ... There are numbers of cytokines, transcription factors and other molecules, that have a role in TH9 differentiation. Cytokines ... All mentioned cytokines then signal through specific transcription factors, which are later on required for a TH9 polarization ...
... was also overexpressed in Stat5/ab and stat 3 which are transcription factors reported to be critical for the growth ...
... mainly because of high level of phosphorylation on key transcription factor, STAT5. In mice, TCM proved to confer more powerful ...
GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also been shown to signal ... Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric ... Root RK, Dale DC (March 1999). "Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: ... CFU-GM Granulocyte-macrophage colony-stimulating factor receptor Filgrastim (Neupogen, a granulocyte colony-stimulating factor ...
STATs (signal transduction and activators of transcription) are members of a family of transcription factors, and they have src ... IL-2 and IL-4 activate JAK1, JAK3 and STAT5. JAK3 activating mutations are found in 16% of T-cell acute lymphoblastic leukemia ... Once activated, the JAKs create docking sites for the STAT transcription factors by phosphorylation of specific tyrosine ... After undergoing JAK-mediated phosphorylation, the STAT transcription factors dimerize, translocate to the nucleus, bind DNA at ...
... which are transcription factors with the ability to modulate cytokine receptors and growth factors. JAK2 phosphorylates the BCR ... Warsch, W; Walz, C; Sexl, V (2014). "JAK of all trades: JAK2-STAT5 as novel therapeutic targets in BCR-ABL1 chronic myeloid ... The Ras/MAPK/ERK pathway relays signals to nuclear transcription factors and plays a role in governing cell cycle control and ... Interactions with the IL-3 receptor also induce the Ras/RAF/MEK/ERK pathway to phosphorylate transcription factors which play a ...
... and can function as a cellular transcription factor. The encoded protein can activate transcription through Pyridine-rich ... Kolonics A, Apáti A, Nahajevszky S, Gáti R, Brózik A, Magócsi M (2002). "Unregulated activation of STAT-5, ERK1/2 and c-Fos may ... "Entrez Gene: USF2 upstream transcription factor 2, c-fos interacting". Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, ... Kurschner C, Morgan JI (Feb 1997). "USF2/FIP associates with the b-Zip transcription factor, c-Maf, via its bHLH domain and ...
In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target ... Stöcklin E, Wissler M, Gouilleux F, Groner B (October 1996). "Functional interactions between Stat5 and the glucocorticoid ... However activated GR can complex with these other transcription factors and prevent them from binding their target genes and ... Chang CJ, Chen YL, Lee SC (October 1998). "Coactivator TIF1beta interacts with transcription factor C/EBPbeta and ...
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which is encoded by the STAT3 gene in ... SOCS3 negatively regulates STAT3 and inhibits other STAT proteins like STAT5 and STAT1. STAT5 is important for regulatory T ... STAT3 is a transcription factor that once activated, moves into the nucleus and binds to specific areas of DNA. By binding to ... This indicates that more research must be done to further understand the role that environmental or other genetic factors may ...
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. ... "OrthoMaM phylogenetic marker: STAT5A coding sequence". Liao, Z; Lutz, J; Nevalainen, MT (February 2010). "Transcription factor ... Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 ...
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth ... Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 ... Signal transducer and activator of transcription 5B is a protein that in humans is encoded by the STAT5B gene. STAT5B orthologs ... Barahmand-Pour F, Meinke A, Groner B, Decker T (May 1998). "Jak2-Stat5 interactions analyzed in yeast". J. Biol. Chem. 273 (20 ...
These two transcription factors then combine with IRF9 to form a complex known as the interferon stimulated gene factor 3 ... and STAT-5. In addition to the JAK/STAT pathway, other pathways such as the MAPK and PI3 kinase pathways have been discovered ... complex (ISGF3). This enters the nucleus and binds to promoter regions, causing transcription of various genes called ...
Members of the signal transducer and activator of transcription (STAT) protein family are intracellular transcription factors ... There are seven mammalian STAT family members that have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B ... STAT+Transcription+Factors at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila Signal-transducer ... Originally, STAT proteins were described as latent cytoplasmic transcription factors as phosphorylation was thought to be ...
The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 and Fos which in turn activate the transcription of ... March 1999). "Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of ... One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in ... Cyclin D dependent monophosphorylated Rb still interacts with E2F transcription factors in a way that inhibits transcription of ...
Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and ... This initiates the STAT5, PIK3 and Ras MAPK pathways. This results in differentiation, survival and proliferation of the ... Erythropoietin is the primary erythropoietic factor that cooperates with various other growth factors (e.g., IL-3, IL-6, ... Hemopoietic growth factors Jehovah's Witnesses and blood transfusions GRCh38: Ensembl release 89: ENSG00000130427 - Ensembl, ...
... stat3 transcription factor MeSH D12.776.476.024.421.400 - stat4 transcription factor MeSH D12.776.476.024.421.500 - stat5 ... stat1 transcription factor MeSH D12.776.476.024.381.500.750 - stat2 transcription factor MeSH D12.776.476.024.381.750 - ... stat1 transcription factor MeSH D12.776.476.024.421.200 - stat2 transcription factor MeSH D12.776.476.024.421.300 - ... transcription factor MeSH D12.776.476.024.421.600 - stat6 transcription factor MeSH D12.776.476.024.500.500 - tnf receptor- ...
The ETV6 gene codes for a transcription factor protein that in mice appears to be required for hematopoiesis and maintenance of ... therefore over-stimulates cell signaling pathways such as STAT5, NF-κB, and Extracellular signal-regulated kinases which ... The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor ... platelet derived growth factor receptor A or alpha-type-platelet derived growth factor receptor) gene with the FIP1L1 gene (see ...
2005). "STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell". FEBS Lett. 579 ( ... Zhu M, John S, Berg M, Leonard WJ (Mar 1999). "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma- ... NMYC interactor (NMI) interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors ... 2005). "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol. 353 ...
... is a member of the ETS transcription factor family. The gene codes for a transcription factor protein, ETV6, which acts to ... STAT5, and extracellular signal-regulated kinases. The FLT3 gene is located on human chromosome 13q12.2. Chromosome ... The product of the ETV6 gene is a member of the ETS transcription factor family; it is required for hematopoiesis and ... Songdej N, Rao AK (2017). "Hematopoietic Transcription Factors Mutations - Important Players in Inherited Platelet Defects". ...
STAT5, and STAT6 transcription factors are activated to elicit downstream signaling events. ... Phosphorylation STATs form transcription factors and activate transcription of appropriate genes. The β chain of IL-15R ... It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of transcription factors ... which leads to phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3) and STAT5.[16] Due ...
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 ... allowing differential transcription of type I IFNs in response to stimuli.[5] In particular, IFNβ contains a κB regulatory site ... with the potential to increase or suppress the transcription of over 2000 different genes.[9] For example, type I IFNs induce ...
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 ... 1999). „Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a ... 2004). „Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and ...
As a result, an IFN-stimulated gene factor 3 (ISGF3) complex forms-this contains STAT1, STAT2 and a third transcription factor ... a nuclear adaptor for STAT5 that also regulates signaling through the C3G/Rap1 pathway.[17] Type I IFNs further activate p38 ... After binding dsRNA, this receptor activates the transcription factors IRF3 and NF-κB, which are important for initiating ... They described these observations in a 1959 publication, naming the responsible factor viral inhibitory factor (VIF).[47] It ...
MC1R gene expression is regulated by the microphthalmia-associated transcription factor (MITF).[28][29] Mutations of the MC1R ... The same report showed that neutralizing antibodies to MC1R prevented phosphorylation of STAT5 by erythropoietin, and that MC2R ... Aoki H, Moro O (September 2002). "Involvement of microphthalmia-associated transcription factor (MITF) in expression of human ... positive regulation of transcription by RNA polymerase II. • positive regulation of protein kinase B signaling. • positive ...
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription ... transcription regulatory region DNA binding. • RNA polymerase II transcription factor activity, sequence-specific DNA binding. ... IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has ... "Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300/CBP ...
STAT5B, STAT5, signal transducer and activator of transcription 5B. Зовнішні ІД. OMIM: 604260 MGI: 103035 HomoloGene: 55718 ... transcription, DNA-templated. • Сигнальна трансдукція. • cellular response to growth factor stimulus. • natural killer cell ... GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity. • DNA binding. • GO:0001077, GO: ... positive regulation of transcription from RNA polymerase II promoter. • transcription from RNA polymerase II promoter. • ...
Signal transducer and activator of transcription 5 (STAT5) refers to two highly related proteins, STAT5A and STAT5B, which are ... Cytokine Growth Factor Rev. 10 (2): 131-57. doi:10.1016/S1359-6101(99)00011-8. PMID 10743504.. .mw-parser-output cite.citation{ ... the phosphorylated STAT5 finally goes on to form either homodimers, STAT5-STAT5, or heterodimers, STAT5-STATX, with other STAT ... STAT5 and cancerEdit. STAT5 has been found to be constitutively phosphorylated in cancer cells,[4] implying that the protein is ...
Deregulated transcription factors in leukemia. „Int J Hematol". 94 (2), s. 134-41, Aug 2011. DOI: 10.1007/s12185-011-0905-9. ... kinaza MAP i STAT5[158][159]. Ekspresja FLT3 prawidłowo występuje głównie w początkowym stadium hematopoezy w komórkach CD34+. ... caudal-type homeobox transcription factor 2), który jest związany z określeniem osi przód-tył podczas rozwoju embrionalnego ... LivioL. Pagano LivioL. i inni, Environmental risk factors for MDS/AML, „Haematologica reports", 2(15), listopad 2006 . ...
MC1R gene expression is regulated by the microphthalmia-associated transcription factor (MITF).[25][26] Mutations of the MC1R ... The same report showed that neutralizing antibodies to MC1R prevented phosphorylation of STAT5 by erythropoietin, and that MC2R ... Aoki H, Moro O (September 2002). "Involvement of microphthalmia-associated transcription factor (MITF) in expression of human ... positive regulation of transcription from RNA polymerase II promoter. • positive regulation of protein kinase B signaling. • ...
Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and ... Zhu M, John S, Berg M, Leonard WJ (January 1999). "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma- ... STAT6+Transcription+Factor at the US National Library of Medicine Medical Subject Headings (MeSH). ... Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (September 1994). "An interleukin-4-induced transcription factor ...
... and the transcription of transcription factors which in turn regulate the transcription of clock genes. Translocations between ... STAT5, and Protein kinase B cell signaling pathways. The FIP1L1 component of FIP1L1-PDGFRA is required for the fusion protein ... Factor interacting with PAPOLA and CPSF1 (i.e, FIP1L1; also termed Pre-mRNA 3'-end-processing factor FIP1) is a protein that in ... end-processing factor. FIP1L1 gene fusions between it and either the platelet-derived growth factor receptor, alpha (PGDFRA) or ...
Ram PA, Waxman DJ (2000). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J ... SOCS3 has been shown to interact with: Erythropoietin receptor, Glycoprotein 130, Insulin-like growth factor 1 receptor, Janus ... mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription ... leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): ...
"Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. ... "Loss of SHIP and CIS recruitment to the granulocyte colony-stimulating factor receptor contribute to hyperproliferative ... There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish ... Ram PA, Waxman DJ (Dec 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms ...
... which goes on to activate certain transcription factors such as NFAT, NF-κB, and AP-1. These transcription factors regulate the ... Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 ... Joseph AM, Kumar M, Mitra D (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 ( ... "Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine ...
In vivo model by Zohar et all showed that CXCL9, drove increased transcription of T-bet and RORγ, leading to the polarization ... Farber JM (July 1990). "A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 ... of Foxp3− type 1 regulatory (Tr1) cells or T helper 17 (Th17) from naive T cells via STAT1, STAT4, and STAT5 phosphorylation. ... and acts as functional receptor for platelet factor 4". The Journal of Experimental Medicine. 197 (11): 1537-49. doi:10.1084/ ...
Ram PA; Waxman DJ (2000). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J ... SOCS2 has been shown to interact with insulin-like growth factor 1 receptor and erythropoietin receptor. GRCh38: Ensembl ... deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b)". Mol. Endocrinol. 16 (6): 1394-406 ... Lopaczynski W (1999). "Differential regulation of signaling pathways for insulin and insulin-like growth factor I." Acta ...
"Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor ... Demoulin JB, Van Roost E, Stevens M, Groner B, Renauld JC (September 1999). "Distinct roles for STAT1, STAT3, and STAT5 in ... Perumal NB, Kaplan MH (2011). "Regulating IL9 transcription in T helper cells". Trends in Immunology. 32 (4): 146-50. doi: ... It was first purified and characterized as a T cell and mast cell growth factor and termed as P40, based on their molecular ...
... stat3 transcription factor MeSH D12.776.157.057.186.400 - stat4 transcription factor MeSH D12.776.157.057.186.500 - stat5 ... stat1 transcription factor MeSH D12.776.157.057.061.500.750 - stat2 transcription factor MeSH D12.776.157.057.061.750 - ... stat1 transcription factor MeSH D12.776.157.057.186.200 - stat2 transcription factor MeSH D12.776.157.057.186.300 - ... transcription factor MeSH D12.776.157.057.186.600 - stat6 transcription factor MeSH D12.776.157.057.500.500 - tnf receptor- ...
New strategy to target transcription factor STAT5 to combat leukaemia. 22.02.2018: Acute myeloid leukaemia (AML) is the most ... Transcription factors like STAT5 are similar to genetic light switches and capable of turning genes on and off. But previous ... it subsequently also disrupts STAT5 activation, nuclear translocation, and STAT5-dependent gene transcription. Bettina ... an important transcription factor for blood cell transformation. Targeting the mutated proteins with small molecular weight ...
PR interacts with FGFR-2 and STAT5 in cells treated with FGF2 or with MPA. pPR and pSTAT5 act as transcription factors (11, 21 ... Physical and functional interactions between STAT5 and Runx transcription factors. J Biochem 2008;143:695-709. ... The STAT family of transcription factors mediates cytokine, growth factor, and hormone responses. Following ligand-receptor ... progesterone activates STAT5 (14, 16), (c) FGF2 activates STAT5 in endothelial cells (9), (d) a dominant negative STAT5 ...
Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of ... Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. ... We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent ... Lothar Hennighausen and colleagues identify 440 mammary-specific super-enhancers in mouse and focus on the STAT5-regulated Wap ...
Health Care New Strategy to Target Transcription… Published: February 23, 2018.Released by University of Veterinary Medicine - ... Transcription factors like STAT5 are similar to genetic light switches and capable of turning genes on and off. But previous ... New Strategy to Target Transcription Factor STAT5 to Combat Leukaemia. / no comments ... it subsequently also disrupts STAT5 activation, nuclear translocation, and STAT5-dependent gene transcription. Bettina ...
... particularly of STAT3 and STAT5) occurs with high frequency in a wide variety of human cancers. We reported recently that the ... STAT5 Transcription Factor * Trans-Activators / physiology* * bcl-X Protein Substances * BCL2L1 protein, human ... Activation of STAT5 triggers proliferation and contributes to anti-apoptotic signalling mediated by the oncogenic Xmrk kinase ... We identified STAT5 activation as being involved in both growth and survival signalling triggered by the Xmrk kinase possibly ...
Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer research, 68,1. pp. 236-248. ... We show here that transcription factor Stat5a/b is active in 95% of clinical hormone-refractory human prostate cancers. We show ... Signal transducer and activator of transcription 5a and 5b (Stat5a/b) is critical for the viability of human prostate cancer ...
The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation The ... Here, the authors use STAT5 protein to assemble its own small molecule inhibitors via Mannich ligation (three-component- ... oncogene STAT5 is involved in cancer cell proliferation. ...
The STAT5 (signal transducer and activator of transcription) protein, which is activated transiently in no … ... granulocyte-macrophage colony stimulating factor), was constitutively activated in cell lines derived from CML patients, even ... The STAT5 (signal transducer and activator of transcription) protein, which is activated transiently in normal myeloid cells by ... Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia Oncogene. 1996 Jul 18;13(2):247-54. ...
Degradation of the Transcription Factors NF-κB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in ... Degradation of the Transcription Factors NF-κB, STAT3, and STAT5 Is Involved in Entamoeba histolytica. -Induced Cell Death in ... Signal transducers and activators of transcription (STATs) comprise a family of transcription factors whose members are ... vascular endothelial growth factor, IL-10, and transforming growth factor [44,45,46,47,48]. In addition to STAT3 and STAT5, ...
We have evidenced a physical and functional interaction between members of two unrelated transcription factor families, Ets-1, ... A Stat5-Ets protein complex was the major inducible DNA-binding complex bound to the human IL-2rE GASd/EBSd motif in long-term ... Coimmunoprecipitation experiments evidenced that a Stat5/Ets-1/2 complex is formed in vivo in absence of DNA. GST-pull down ... These results suggest that the inducible Stat5-Ets protein interaction plays a role in the regulation of gene expression in ...
STAT3 Transcription Factor/genetics , STAT5 Transcription Factor/genetics , Signal Transduction ... Degradation of the Transcription Factors NF-kappaB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in ... Degradation of the Transcription Factors NF-kappaB, STAT3, and STAT5 Is Involved in Entamo ... In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death ...
Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells. January 23, 2018. ... Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to several hematopoietic ... These properties are reliant on constitutive account activation of the transcription aspect Stat5 and can end up being ... Amazingly, an 11-residue Stat5-holding peptide (residues 988-998) covered up Stat5 activity in Ba/Y3 cells and growth and ...
Signal transducer and activator of transcription 5B. *STA5B_HUMAN. *STAT5. *Stat5b. *Transcription factor STAT5B ... Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL- ... Carries out a dual function: signal transduction and activation of transcription. ...
Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation. ... The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are ... STAT transcription factor, all-alpha domain (IPR013800). Short name: STAT_TF_alpha ... GO:0006355 regulation of transcription, DNA-templated GO:0007165 signal transduction Molecular Function. No terms assigned in ...
Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation. ... Transcription factor STAT (IPR001217). Short name: STAT Overlapping homologous superfamilies *STAT transcription factor, DNA- ... The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are ... GO:0006355 regulation of transcription, DNA-templated GO:0007165 signal transduction Molecular Function. GO:0003700 DNA-binding ...
Signal Transducer And Activator Of Transcription 5B, including: function, proteins, disorders, pathways, orthologs, and ... DNA-binding transcription factor activity, RNA polymerase II-specific. ISM. 19274049. GO:0001228. DNA-binding transcription ... NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-helical region of the STAT5 ... Transcription Factor. Binding Sites. Gene Targets. GH17J042266. Promoter/Enhancer. 2.7. EPDnew FANTOM5 Ensembl ENCODE ...
Belongs to the transcription factor STAT family.. Contains 1 SH2 domain.. * Post-translational. modifications. Tyrosine ... Signal transducer and activator of transcription 5B antibody. *STA5B_HUMAN antibody. *STAT5 antibody ... Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL- ... Carries out a dual function: signal transduction and activation of transcription. ...
Transcription Factors STAT5 and STAT3 Zoran Culig, Richard G. Pestell, Marja T. Nevalainen ...
0/STAT5 Transcription Factor; 0/Trans-Activators; 12629-01-5/Human Growth Hormone; 67763-96-6/Insulin-Like Growth Factor I; EC ... STAT5 Transcription Factor. Sex Characteristics. Signal Transduction / physiology*. Trans-Activators / physiology. Grant ... Insulin-Like Growth Factor I / physiology. Islets of Langerhans / physiology. Janus Kinase 2. Liver / metabolism. Milk Proteins ... 10537136 - Dissociation of janus kinase 2 and signal transducer and activator of transcription 5 a.... 24951756 - The atypical ...
STAT5 Transcription Factor. Signal Transduction / drug effects. T-Lymphocytes, Cytotoxic / cytology*, drug effects*, enzymology ... 0/STAT5 Transcription Factor; 0/Trans-Activators; 11096-26-7/Erythropoietin; EC 2.7.1.-/MAP2K1 protein, human; EC 2.7.1.-/ ... In T-ER transformants expressing JAK2 (T-JER), EPO induced tyrosine phosphorylation of the EPOR, JAK2, and STAT5, and ... 8308069 - Transient effect of epidermal growth factor on the motility of an immortalized mammary .... 15170659 - Monolayer ...
Stat5 is a transcription factor - a protein that can regulate expression of other genes. In 2003, Dr. Nevalainen discovered ... Nevalainen found that excess Stat5 in prostate cancer cells is linked to metastasis, and excess Stat5 expression predicts early ... "Our latest findings on Stat5 provide further support for the idea that targeting Stat5 protein pharmacologically might provide ... Biomedical Science »Cancer »Medical Wellness »Stat5 »amplification »cancer cells »health services »human prostate cancer » ...
New strategy to target transcription factor STAT5 to combat leukaemia. Acute myeloid leukaemia is the most common type of acute ... Add broken DNA repair to the list of inherited colorectal cancer risk factors. An analysis of nearly 3,800 colorectal cancer ... HealthDay)-Cancer history has an important impact on mortality independent of cardiovascular risk factors (CVRFs), according to ...
signal transducer and activator of transcription 5B. *STAT5. *STAT5b. *transcription factor STAT5B ... What is STAT6?The cellular pathway comprising tyrosine kinase Janus Kinase (JAK) and the transcription factor STAT connect ... Signal Transducer and Activator of Transcription STAT6: More than a Player in Allergic Inflammation. By Jamshed Arslan, Pharm. ...
... substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A ( ... STAT5 belongs to the STAT gene family of transcription factors [19]. STAT5 comprises two highly homologous isoforms; the 94 kDa ... 2008) Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res 68: 236-248. * View ... 2003) Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol Chem 278: 27287-27292 ...
0 (Il2rb protein, mouse); 0 (Interleukin-2); 0 (Interleukin-2 Receptor beta Subunit); 0 (STAT5 Transcription Factor); EC 2.3. ... In turn, the truncated form of Stat5 prevents transcription of the full-length form of Stat5. We also demonstrate that CBP ... STAT5 Transcription Factor); 156986-95-7 (Receptor, Interferon alpha-beta); 82115-62-6 (Interferon-gamma). ... Fator de Transcri o STAT5/bioss ntese. Fator de Transcri o STAT5/gen tica. Viremia/sangue. Viremia/virologia. ...
The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this ... STAT5 Transcription Factor); 0 (Trans-Activators); 0 (Zfpn1a1 protein, mouse); 0 (interferon regulatory factor-4); 0 (proto- ... Kruppel-Like Transcription Factors); 0 (Nerve Tissue Proteins); 0 (PAX5 Transcription Factor); 0 (Pax5 protein, mouse); 0 ( ... STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers ...
STAT5 is a transcription factor involved in signal transduction pathways inducing anti-apoptotis and proliferation. From ... 3 and 5 expression in melanoma metastasis by immunohistochemistry and evaluate activation of the transcription factors by the ... Recent publications revealed that neoantigens of the tumor might be one of the main factors to lead to recognition by the ... In interferon resistant melanoma cell lines we found a high expression of STAT5 and a low expression of STAT1. Hence, this ...
Critical role of STAT5 transcription factor tetramerization for cytokine responses and normal immune function. Immunity 36: 586 ... and the two most important transcription factors are GATA3 and STAT5 (33). Although early Th2 differentiation requires GATA3, ... proteins and the transcription factor CSL/RBP-Jk (encoded by Rbpj) to induce target gene transcription HES genes in mammals. ... at least in part due to Notch-induced transcription of Gata3, a Th2-specific transcription factor (11, 13). The activation of ...
  • Constitutively activated forms of STAT3 and STAT5 have been observed in tumor-derived cell lines and human cancer ( 12 ). (aacrjournals.org)
  • Extensive studies of primary tumors and tumor derived cell lines revealed that inappropriate activation of specific STATs (particularly of STAT3 and STAT5) occurs with high frequency in a wide variety of human cancers. (nih.gov)
  • Moreover, incubation with amoebae resulted in marked degradation of STAT proteins (STAT3 and STAT5) and NF-κB (p65) in Caco-2 cells. (parasitol.kr)
  • Stat3 and Stat5) is associated with cellular transformation. (ebi.ac.uk)
  • As an alternative strategy, the team investigated transcription factors Stat3 and Stat5, which are linked to bcr/abl-induced transformation. (thaindian.com)
  • The team tested whether Stat3 and Stat5, acting downstream of Bcr-Abl are critical for leukaemia maintenance and if they could be a alternative target for treatment. (thaindian.com)
  • The transcription factors and proto-oncogenes STAT3 and STAT5 are highly activated in hematological malignancies and represent promising therapeutic targets. (mdpi.com)
  • Players of the JAK/STAT pathway-in particular STAT3 and STAT5-have been repeatedly shown to represent such critical factors [ 4 , 5 , 6 , 7 , 8 ]. (mdpi.com)
  • STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. (bloodjournal.org)
  • Following their phosphorylation by JAKs, STAT proteins translocate to the nucleus where they bind to DNA and regulate transcription of specific genes in a cell type- and cytokine-specific manner. (fishersci.com)
  • Cytokines such as IL-3, IL-5, and GM-CSF that signal via the common beta chain induce STAT5 phosphorylation on tyrosine 694 by JAK 2. (fishersci.com)
  • Phosphorylation of STAT5 on tyrosine 694 is essential for STAT5 dimer formation, nuclear translocation, and DNA binding activity. (fishersci.com)
  • In T-ER transformants expressing JAK2 (T-JER), EPO induced tyrosine phosphorylation of the EPOR, JAK2, and STAT5, and consequently STAT5-responsive genes including bcl-X and cis1 were normally induced. (biomedsearch.com)
  • Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. (aacrjournals.org)
  • Activation of interferon regulatory factor 5 by site specific phosphorylation. (nih.gov)
  • After phosphorylation by JAK tyrosine kinases, STATs enter the nucleus to regulate transcription of many different genes. (acris-antibodies.com)
  • After phosphorylation, STAT1 and STAT2 form heterodimers that function as more potent inducers of transcription than the STAT1 homodimer. (acris-antibodies.com)
  • To investigate the mechanism of CYP3A4 mRNA upregulation, we analyzed the phosphorylation of STAT5 after celecoxib treatment and found it to be significantly increased. (aspetjournals.org)
  • Phosphorylation at Tyr694 is obligatory for Stat5 activation. (biomol.com)
  • Stat5 is localized in the cytoplasm and upon phosphorylation at Y694 is translocated to the nucleus. (biomol.com)
  • Identification of growth hormone receptor (GHR) tyrosine residues required for GHR phosphorylation and JAK2 and STAT5 activation. (eu.org)
  • The data revealed that Janus kinases (JAKs) couple IL-2 receptors to the coordinated phosphorylation of transcription factors, regulators of chromatin, mRNA translation, GTPases, vesicle trafficking, and the actin and microtubule cytoskeleton. (babraham.ac.uk)
  • In some individuals, decreased signal transducer and activator of transcription 5 phosphorylation correlated with significantly higher expression of protein tyrosine phosphatase N2, a negative regulator of IL-2R signaling. (diabetesjournals.org)
  • Engagement of the IL-2R results in a cascade of signaling events initiated by phosphorylation of the tyrosine kinases Janus kinase 1 (JAK1) and JAK3 followed by phosphorylation of tyrosine residues on the IL-2R β-chain that results in phosphorylation of STAT5 and Shc. (diabetesjournals.org)
  • Examples of these pathways are the direct phosphorylation of BRAF and Stat5, as well as the enhanced transcription of C-myc. (uni-wuerzburg.de)
  • These lines will help to elucidate questions that are still remaining in Stat5 biology and its function in melanoma progression, like the role of Stat5 phosphorylation on tumor invasiveness. (uni-wuerzburg.de)
  • Transcription factors like STAT5 are similar to genetic light switches and capable of turning genes on and off. (vetmeduni.ac.at)
  • This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. (aacrjournals.org)
  • Also, a clear cross talk between growth factors that input to STAT5 and PR on genes containing GAS sequences has been shown in human breast cancer cells ( 14, 15 ). (aacrjournals.org)
  • Activation of Stat5 by many cytokines implies that it cannot alone insure the specificity of the regulation of its target genes. (archives-ouvertes.fr)
  • The study, reported in the May 7 issue of the American Journal of Pathology, found a direct association between the number of Stat5 genes in human prostate cancer cells and Stat5 protein levels, and also revealed that gene amplification and protein levels increased as prostate cancer metastasized and became resistant to castration (anti-androgen) therapy. (innovations-report.com)
  • Stat5 is a transcription factor - a protein that can regulate expression of other genes. (innovations-report.com)
  • Once activated, Notch intracellular domain translocates to the nucleus, where it interacts with Mastermind-like (MAML) proteins and the transcription factor CSL/RBP-Jk (encoded by Rbpj ) to induce target gene transcription HES genes in mammals. (jimmunol.org)
  • GH-stimulated activation of signal transducers and activators of transcription (STATs), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3' kinase (PI3K) cascades have been shown to regulate the transcription of GH-responsive genes. (biomedsearch.com)
  • Many Ras responsive genes harbor combinatorial Ets/AP1 recognition motifs through which Ets1 and AP1 synergistically activate transcription when stimulated by Ras. (wikipedia.org)
  • Male-specific hepatic Bcl6: growth hormone-induced block of transcription elongation in females and binding to target genes inversely coordinated with STAT5. (semanticscholar.org)
  • Characterization of STAT5a, LSD1 and HDAC3 target genes by ChIP-seq and RNA-seq revealed gene subsets regulated by independent or combined action of the factors and LSD1/HDAC3 to play dual role in their activation or repression. (nih.gov)
  • These genes exhibited increased binding frequency in promoters, and in conjunction with the absence of GAS sites, the data indicate a requirement for stabilization by additional factors, which might recruit LSD1/HDAC3. (nih.gov)
  • Two closely related variants of Stat5, Stat5a and Stat5b, are encoded by distinct genes. (asm.org)
  • 1 Hypoxia stabilizes the transcription factor Hif-1 and thereby induces and promotes the expression of several genes containing hypoxia responsive elements in their regulatory region: proangiogenic factors like vascular endothelial growth factor (VEGF) or stromal-cell derived factor-1α (SDF-1α, CXCL12), 2 vasoconstrictors like endothelin-1 as well as inflammation-associated genes such as inducible NO synthase 3 and Cox2. (ahajournals.org)
  • The promoter regions are assumed to be within ∼1 kb upstream of the starting transcription site (for the known genes) or the first ATG (for the predicted genes). (wikiversity.org)
  • GAs trigger the expression of hydrolytic enzymes through transcription activation of corresponding genes (Jacobsen et al. (wikiversity.org)
  • 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)
  • We have also identified STAT5 target genes in adipocytes. (pbrc.edu)
  • All of our studies demonstrate that STAT5 is an important transcription factor in adipocytes and can regulate genes associated with Type 2 Diabetes. (pbrc.edu)
  • In breast cancer cells, the ABL kinases activated the transcriptional coactivator TAZ and the transcription factor STAT5, which triggered the transcription of genes encoding factors that activate osteoclasts (cells that break down bone) and those that enhance the survival of breast cancer cells in the bone microenvironment. (sciencemag.org)
  • ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast-activating factors interleukin-6 (IL-6) and matrix metalloproteinase 1 (MMP1). (sciencemag.org)
  • not only are multiple genes involved in its pathogenesis, but additional environmental factors such as diet and inflammation are also involved. (bmj.com)
  • The exhaustive research into prostate cancer to date has demonstrated a complex interaction of multiple genes and environmental factors, some of which may be more important in individual prostate cancer cases. (bmj.com)
  • STAT5 is coded for by two genes, STAT5A and STAT5B . (b-s-h.org.uk)
  • C-myc is a transcription factor that is thought to regulate the expression of approximately 15% of all human genes and is involved in cancer progression of a large number of different tumors. (uni-wuerzburg.de)
  • Researchers led by Richard Moriggl, director of the Ludwig Boltzmann Institute for Cancer Research and Professor for Functional Cancer Genomics in a joined appointment to the University of Veterinary Medicine, Vienna and Medical University Vienna chose to target the SH2 domain of STAT5, which is essential for the interactions between STAT5 proteins and their subsequent activity. (vetmeduni.ac.at)
  • The researchers aimed at development, synthesis and preclinical testing of a new compound that targets the oncogenic functions of STAT5 proteins. (vetmeduni.ac.at)
  • STAT5 ( 16 ), PR ( 17 ), or FGFR-2 ( 5 ) disrupted mammary gland-displayed branching and lobuloalveolar defects, suggesting a link between these proteins in the mammary gland. (aacrjournals.org)
  • These properties are reliant on constitutive account activation of the transcription aspect Stat5 and can end up being antagonized by the SH2 domain-containing proteins phosphatase SHP-1. (researchreportone.com)
  • Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. (ebi.ac.uk)
  • The amino acid sequences of STAT5 alpha and STAT5 beta show 96% sequence similarity, and both proteins are co expressed in most tissues in virgin and lactating mice. (thermofisher.com)
  • Upon binding to their cellular receptors, hematopoietic growth factors and cytokines activate Janus-activated kinase (JAK) proteins. (aacrjournals.org)
  • The CaM-regulated basic helix-loop-helix family of transcription factors was reported in mammals, where CaM inhibits the protein-DNA interaction by competing with the DNA-binding domain in certain proteins (16). (wikiversity.org)
  • These proteins are signaling molecules and transcription factors, which means they control the gene expression in a tissue specific manner. (pbrc.edu)
  • To further understand the biology of this multifunctional protein, we are identifying other proteins that associate with STAT5 and are studying a mouse model that lacks STAT5 proteins in adipose tissue. (pbrc.edu)
  • Able, A.A., Burrell, J.A., and Stephens, J.M. (2017) STAT5 interacting proteins: A synopsis of proteins that regulate STAT5 activity. (pbrc.edu)
  • Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. (bloodjournal.org)
  • The STAT proteins (signal transducer and activator of transcription) comprise a family of transcription factors. (merckmillipore.com)
  • STAT5B (Signal Transducer And Activator Of Transcription 5B) is a Protein Coding gene. (genecards.org)
  • This STAT5b-mediated inhibitory effect on NF-kB signaling does not depend on STAT5b-DNA interactions but requires the carboxyl terminus of STAT5b as well as STAT5b nuclear translocation and/or accumulation, suggesting that STAT5b is competing for a nuclear factor(s) necessary for NF-kB-mediated activation of target promoters. (acris-antibodies.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)
  • Sequence analysis revealed a higher similarity between both Stat5 sequences when compared to either human Stat5a or Stat5b. (uni-wuerzburg.de)
  • Signal transducer and activator of transcription 5a and 5b (Stat5a/b) is critical for the viability of human prostate cancer cells. (unibas.ch)
  • The STAT5 (signal transducer and activator of transcription) protein, which is activated transiently in normal myeloid cells by cytokines such as GM-CSF (granulocyte-macrophage colony stimulating factor), was constitutively activated in cell lines derived from CML patients, even in the absence of GM-CSF. (nih.gov)
  • Cell surface area receptors guaranteed by these ligands activate many signaling paths including the Jak-Stat (sign transducer and activator of transcription) path. (researchreportone.com)
  • Description: This SRBCZX monoclonal antibody recognizes signal transducer and activator of transcription 5 (STAT5) when phosphorylated on tyrosine 694. (fishersci.com)
  • In the current study, we demonstrate that the signal transducer and activator of transcription 5 (Stat5) is rapidly activated by IgE cross-linkage, and that its expression is critical to the MC response. (jimmunol.org)
  • 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 replication and transcription activator of murine gammaherpesvirus 68 cooperatively enhances cytokine-activated, STAT3-mediated gene expression. (nih.gov)
  • Signal transducer and activator of transcription 5 (Stat5) belongs to a family of cytoplasmic. (biomol.com)
  • Signal transducer and activator of transcription 5 (Stat5) belongs to a family of cytoplasmic transcription factors that can be activated (phosphorylated) by a cell surface receptor. (biomol.com)
  • Via these structures, among others, the signal transducer and activator of transcription 5 (STAT5) is recruited and activated. (ahajournals.org)
  • Unexpectedly, Wip1 allows steroid hormone-receptor-positive cells but not alveolar progenitors to activate STAT5 (signal transducer and activator of transcription 5) in the virgin state. (nih.gov)
  • In the absence of Wip1, hormone-receptor-positive cells have significantly reduced transcription of RANKL (receptor activator of nuclear factor kappa-B ligand) and IGF2 (insulin-like growth factor 2), paracrine stimulators of alveolar development. (nih.gov)
  • The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. (rupress.org)
  • IL-2 regulates FOXP3 expression in a signal transducer and activator of transcription 5 (STAT5)-dependent manner ( 6 ), and both IL-2 and STAT5 are required for the peripheral generation of iTregs ( 5 , 7 ) and maintenance of nTregs ( 8 , 9 ). (diabetesjournals.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)
  • Knockdown of KLF13 also reduced the level of the transcription factor signal transducer and activator of transcription 5, which led to the downregulation of the ataxia-telangiectasia mutated DNA damage pathway and the chemokine interleukin-8 (IL-8). (ovid.com)
  • now show that when oligodendrocytes are activated by MP, glucocorticoid receptors interact with the signal transducer and activator of transcription STAT5. (jneurosci.org)
  • Children with a record of hospitalisation for severe RSV bronchiolitis demonstrated markedly lower levels of DNA methylation at two cytosine-phosphate-guanine dinucleotide (CpG) loci of the PRF1 proximal enhancer, corresponding to a signal transducer and activator of transcription 5 (STAT5) responsive element, compared to controls, adjusted odds ratios of 0.82 (95% confidence interval [CI] 0.71, 0.94) and 0.73 (95% CI 0.58, 0.92) for each 1% increase in DNA methylation. (biomedcentral.com)
  • The STAT family of transcription factors mediates cytokine, growth factor, and hormone responses. (aacrjournals.org)
  • Wakao, H., Gouilleux, F. & Groner, B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. (nature.com)
  • Results using BCR-ABL mutants which specifically uncouple connections to known signal transduction pathways show that STAT5 activation is kinase dependent and correlates directly with ability to confer cytokine independent growth in hematopoietic cells. (nih.gov)
  • Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. (abcam.com)
  • Stat5-deficient (Stat5KO) MC demonstrated a significant decrease in IgE-mediated degranulation, leukotriene B 4 production, cytokine secretion, and survival signals. (jimmunol.org)
  • Our work demonstrates that Stat5 is a critical factor in IgE-induced MC activation, acting in part via posttranscriptional control of cytokine mRNA stability. (jimmunol.org)
  • These drugs target growth factor- and cytokine-activated signal transduction pathways, thereby disrupting extracellular and intracellular signals that stimulate proliferation and provide these cells with a survival advantage. (aacrjournals.org)
  • Also, another cytokine-dependent signaling, an extrinsic apoptosis pathway associated with the family of tumor necrosis factor (TNF) receptors, has been investigated. (intechopen.com)
  • In addition, we consider cytokine-dependent pathways of apoptosis regulation (STAT-signaling pathway and tumor necrosis factor (TNF)-dependent pathway). (intechopen.com)
  • By studying how engagement of cytokine receptors transduce signals that, in turn, regulate transcription factors and epigenetic events to modulate gene expression, we hope to understand, more in depth, how T cells participate in host defense and contribute to the pathogenesis of immune-mediated diseases. (nih.gov)
  • MIIB demonstrated that IL-12 activates STAT4, a key factor that initiates the development of Th1 cells that produce the signature cytokine interferon-γ (IFN-γ). (nih.gov)
  • The emphasis of our research is on theoretical and medical problems related to the role of transcription factors (STAT5) that mediate cytokine action and histone methyltransferases (EZH1 and EZH2). (nih.gov)
  • LGP scientists have discovered that cytokine-STAT5 signaling is essential for the establishment of mammary alveolar progenitor cells (Yamaji et al. (nih.gov)
  • IL-2 is a T-cell growth factor and key cytokine involved in immune regulation that is produced in a transient manner primarily by activated effector T-cells ( 4 ). (diabetesjournals.org)
  • Reconstitution experiments in non-hematopoietic cells show that STAT5 activation by BCR-ABL occurs independent of cytokines. (nih.gov)
  • These findings are consistent with a role for STAT5 in hematopoietic transformation by BCR-ABL. (nih.gov)
  • Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to several hematopoietic malignancies including myeloproliferative neoplasm (MPN). (researchreportone.com)
  • Amazingly, an 11-residue Stat5-holding peptide (residues 988-998) covered up Stat5 activity in Ba/Y3 cells and growth and myeloid difference Rabbit polyclonal to AKAP5 of hematopoietic control/progenitor cells. (researchreportone.com)
  • As a result, this research additional defines PLC-3-CT as the Stat5- and SHP-1-holding domains by determining minimal useful sequences of PLC-3 for its growth suppressor function and suggests their potential application in the control of hematopoietic malignancies. (researchreportone.com)
  • In the intima media, monocytes acquire a phenotype that is consistent with inflammatory macrophages and inflammatory DCs and is influenced by load of modified lipids, cytokines, chemokines, and hematopoietic growth factors. (frontiersin.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)
  • It has been proposed that paracrine factors participate in the activation of hormone receptors to support hormone-independent tumor growth. (aacrjournals.org)
  • They previously found that MP binds to glucocorticoid receptors and increases transcription of bcl-X L , an anti-apoptotic protein. (jneurosci.org)
  • FGFRs trigger the activation of multiple pathways ( 8 ) and the activation of SRC, Janus kinase 2 (JAK2), and Signal transducers and activators of transcription (STATs) has recently been reported ( 9 ). (aacrjournals.org)
  • STAT5 is a transcription factor involved in signal transduction pathways inducing anti-apoptotis and proliferation. (uni-heidelberg.de)
  • Among these, the AKT and STAT5 pathways appear most critical and may result in drug-resistant chronic myeloid leukemia and systemic mastocytosis. (haematologica.org)
  • For many years now, Moriggl has been researching signalling pathways that switch on the family of STAT transcription factors. (meduniwien.ac.at)
  • IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter. (sciencemag.org)
  • Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9-expressing cells. (aacrjournals.org)
  • One of the key problems in conducting studies to identify growth factors and signaling pathways that can replace androgens in the growth control of prostate cancer cells is the lack of androgen receptor (AR)-positive human prostate cancer cell lines that are regulated by androgens and would be tumorigenic in nude mice. (aacrjournals.org)
  • Xmrk is an orthologue of the human epidermal growth factor receptor (EGFR) and activates several downstream signaling pathways. (uni-wuerzburg.de)
  • Activating mutations in the receptor FLT3 represent 30% of driver mutations in AML, which in turn activates STAT5, an important transcription factor for blood cell transformation. (vetmeduni.ac.at)
  • Binds to the GAS element and activates PRL-induced transcription. (abcam.com)
  • In the liver, growth hormone activates STAT5. (meduniwien.ac.at)
  • In the MMTV-neu model, HER2/neu activates STAT5 in alveolar progenitor cells independent of Wip1, but HER2/neu does not override the defect in STAT5 activation in Wip1-deficient hormone-sensing cells, and paracrine stimulation remains attenuated. (nih.gov)
  • The IL-2 receptor couples to JAK tyrosine kinases and activates the STAT5 transcription factors. (babraham.ac.uk)
  • The following antibody was used in this experiment: Phospho-STAT5 alpha (Tyr694) Recombinant Rabbit Monoclonal Antibody (6H5L15) from Thermo Fisher Scientific, catalog # 701063, RRID AB_2532365. (thermofisher.com)
  • The following antibody was used in this experiment: Phospho-STAT5 (Tyr694) Monoclonal Antibody (SRBCZX), APC, eBioscience™ from Thermo Fisher Scientific, catalog # 17-9010-42, RRID AB_2573272. (thermofisher.com)
  • But previous strategies to target STAT transcription factors have been difficult and failed on potency or a lack of specificity. (vetmeduni.ac.at)
  • We also found a new mechanism of activation of STAT5 by receptor tyrosine kinases, whereby direct interaction of the receptor kinase domain with the STAT protein in a phosphotyrosine independent way led to activation of STAT5 in terms of DNA binding and target gene expression. (nih.gov)
  • Competition with GAS- and EBS-specific oligonucleotides and immunoassays with a set of anti-Stat and anti-Ets families revealed that the IL-2-induced Stat5-Ets complex recognizes several GAS motifs identified as target sites for activated Stat5 dimers. (archives-ouvertes.fr)
  • Among seven mammalian Stat protein (1C4, 5A, 5B, and 6), Stat5 encoded by two connected genetics carefully, and rodents develop a late-onset MPN [16]. (researchreportone.com)
  • Belongs to the transcription factor STAT family. (abcam.com)
  • 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 protein encoded by this gene is a member of the STAT family of transcription factors. (genecards.org)
  • 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. (genecards.org)
  • STAT5 alpha is a member of the STAT family of transcription factors. (fishersci.com)
  • Natural killer (NK) cells are tightly regulated by the JAK-STAT signaling pathway and cannot survive in the absence of STAT5. (aacrjournals.org)
  • On both the WAP CoRE and the mouse mammary tumor virus long terminal repeat promoter, the NFI-B isoform preferentially activated gene transcription in cooperation with STAT5A and GR. In contrast, the NFI-A isoform suppressed GR and STAT cooperativity at the WAP CoRE. (asm.org)
  • Acris Antibodies offers a wide range of antibodies to STAT Transcription Factors. (acris-antibodies.com)
  • ASCs favored STAT3 over STAT5 transcription factor binding on STAT binding sites within the IL-17A/F gene locus. (diabetesjournals.org)
  • 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)
  • The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. (bloodjournal.org)
  • In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. (bloodjournal.org)
  • The most common molecular cause is FLT3 mutations, which result in hyper-activation of STAT5. (vetmeduni.ac.at)
  • In the study now reported in the prestigious Nature Group journal Leukemia, the compound not only binds directly to STAT5, it subsequently also disrupts STAT5 activation, nuclear translocation, and STAT5-dependent gene transcription. (vetmeduni.ac.at)
  • We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. (aacrjournals.org)
  • We reported recently that the melanoma inducing EGFR-related receptor Xmrk specifically induces constitutive activation of STAT5 in fish melanoma cells. (nih.gov)
  • We identified STAT5 activation as being involved in both growth and survival signalling triggered by the Xmrk kinase possibly due to STAT5 induced expression of pim-1 and bcl-x. (nih.gov)
  • Carries out a dual function: signal transduction and activation of transcription. (abcam.com)
  • Finally, we identified STAT5-binding cis -acting regulatory element activation as a critical driver of Lfng transcriptional activation. (jimmunol.org)
  • Activation of STAT5 alpha in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. (fishersci.com)
  • These experiments revealed an essential role for Stat5 in IgE-mediated activation that impacts our understanding of MC-mediated inflammatory responses, possibly revealing a new clinical target for MC-associated diseases. (jimmunol.org)
  • It is widely accepted that activation domains of these liver-enriched transcription factors directly facilitate the assembly of ubiquitous transcription factors and RNA polymerase II onto the promoter ( Ptashne and Gann, 1990 ). (aspetjournals.org)
  • STAT5 has been shown to be the essential mediator of prolactin induced milk protein gene activation. (acris-antibodies.com)
  • Recently, it was revealed that celecoxib upregulates the expression of CYPs to normal levels through the activation of signal transducer and transcriptional activation factor 5 (STAT5). (aspetjournals.org)
  • Aberrant Stat5 activation has been implicated in the pathogenesis of chronic myelogenous leukemia, prostate and breast cancer and tumor metastasis. (biomol.com)
  • Upon activation, Jaks phosphorylate receptor subunits, thereby providing docking sites for downstream signaling molecules, such as the signal transducers and activators of transcription (STATs). (nih.gov)
  • A single phosphotyrosine residue of the prolactin receptor is responsible for activation of gene transcription. (eu.org)
  • Identification of tyrosine residues in the intracellular domain of the growth hormone receptor required for transcriptional signaling and Stat5 activation. (eu.org)
  • Integrated RNA sequencing, chromatin immunoprecipitation sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) revealed that STAT5 and HOXA9 have co-occupancy across the genome, resulting in enhanced STAT5 transcriptional activity and ectopic activation of FOS/JUN (AP1). (aacrjournals.org)
  • Together, these data emphasize the essential role of IL-2/IL-2R signaling-and specifically, STAT5 activation-in peripheral tolerance mediated by Tregs. (diabetesjournals.org)
  • Study co-leader Veronika Sexl said: "What is exciting is that in recent years cases have been found of patients with mutations that result in STAT5 activation and are assumed to drive disease. (b-s-h.org.uk)
  • Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. (nature.com)
  • We recently showed that the transcription factor Stat5 is essential for MC survival and proliferation in vitro and in vivo ( 10 ). (jimmunol.org)
  • Thus, Stat5 expression is not required for normal MC development but is necessary to support subsequent survival and proliferation. (jimmunol.org)
  • Our experiments define STAT5 as a master regulator of NK-cell proliferation and lytic functions. (aacrjournals.org)
  • Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). (aacrjournals.org)
  • Using a model in which LAG-3 blockade or absence reliably augmented homeostatic proliferation in vivo, we found that IL-2 and STAT5 are critical for LAG-3 function. (nih.gov)
  • 2012). These studies will provide insight into mechanisms used by STAT5 to control lineage decision-making, cell proliferation and differentiation. (nih.gov)
  • STAT5 is a transcription factor that is absolutely essential for peripheral T cell proliferation. (furman.edu)
  • Following T cell receptor (TCR) engagement, activated T cells produce IL-2 which induces proliferation via STAT5. (furman.edu)
  • A synthetic phospho-peptide corresponding to residues surrounding Tyr694 of human Stat5 was used as immunogen. (biomol.com)
  • We have recently shown, by using a medroxyprogesterone acetate (MPA)-induced murine breast cancer model ( 2 ), that fibroblast growth factor 2 (FGF2) is highly expressed in the stroma of hormone-independent carcinomas and that the FGF receptor (FGFR) inhibitor PD173074 decreased tumor growth ( 3 ). (aacrjournals.org)
  • Mechanistically, BATF controlled the formation of colon-infiltrating, IL-7 receptor-positive (IL-7R+), granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+), donor T effector memory (Tem) cells. (jci.org)
  • Point mutations in the binding sites for specific transcription factors present within this CoRE have demonstrated the importance of both nuclear factor I (NFI) and STAT5 as well as cooperative interactions with the glucocorticoid receptor (GR) in the regulation of WAP gene expression in the mammary gland of transgenic mice. (asm.org)
  • Moreover, LPS produced a rapid and profound decrease in nuclear binding activity to the mouse Oatp4 putative response elements for hepatocyte nuclear factor (HNF) 1, CAAT/enhancer binding protein (C/EBP), HNF3, and heterodimers of retinoid X receptor (RXR) and retinoic acid receptor (RAR). (aspetjournals.org)
  • STAT5 has been theorized to be the physiological substrate of the insulin receptor. (acris-antibodies.com)
  • This study reveals the molecular regulation mechanisms of neurosecretory cell apoptosis in physiological and pathological (oncogene human epidermal growth factor receptor (HER)-2/Neu overexpression) aging. (intechopen.com)
  • Later on in life, tumors arise that are mostly steroid-receptor positive, although a small subset of tumors overexpressing human epidermal growth factor 2 (HER2) and some lacking estrogen receptor, progesterone receptor (PR), and HER2 (triple negative) are present, as is the situation in humans. (frontiersin.org)
  • Another transcription factor implicated in lipogenesis is the peroxisome proliferator activated receptor γ. (embopress.org)
  • In other cell types, the transcriptional effects of glucocorticoids are determined by whether the activated receptor binds directly to glucocorticoid response elements in promoters or first interacts with other transcription factors and bind to those factors' response elements. (jneurosci.org)
  • 2011) Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range. (els.net)
  • 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)
  • 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)
  • The discovery also suggests that testing Stat5 gene amplification in patients could provide a biomarker that identifies those patients most likely to respond to Stat5 inhibition, Dr. Nevalainen says. (innovations-report.com)
  • Thus, inhibition of Stat5 may provide a novel therapeutic approach for treatment of leukaemia," said Sexl. (thaindian.com)
  • A Stat5-Ets protein complex was the major inducible DNA-binding complex bound to the human IL-2rE GASd/EBSd motif in long-term proliferating normal human T cells activated by CD2 and CD28. (archives-ouvertes.fr)
  • These results suggest that the inducible Stat5-Ets protein interaction plays a role in the regulation of gene expression in response to IL-2 in human T lymphocytes. (archives-ouvertes.fr)
  • An international group of investigators, led by researchers at Thomas Jefferson University's Kimmel Cancer Center, have solved the mystery of why a substantial percentage of castrate-resistant metastatic prostate cancer cells contain abnormally high levels of the pro-growth protein Stat5. (innovations-report.com)
  • Our latest findings on Stat5 provide further support for the idea that targeting Stat5 protein pharmacologically might provide powerful therapy for advanced prostate cancer," she says. (innovations-report.com)
  • Dr. Nevalainen has long studied Stat5 in prostate cancer, and with her colleagues, has authored a number of crucial studies demonstrating the impact the gene and its protein can have on prostate cancer progression. (innovations-report.com)
  • Stat5 isn't the only protein that drives prostate cancer, but it is a very important one," she says. (innovations-report.com)
  • In 2003, Dr. Nevalainen discovered that Stat5 protein is critical for viability of prostate cancer cells and growth of prostate tumors in mice. (innovations-report.com)
  • While it is known that excess Stat5 protein predicts early recurrence of prostate cancer, development of metastatic disease and death from prostate cancer, researchers will need to determine if Stat5 gene amplification is also linked to those outcomes, she adds. (innovations-report.com)
  • The mouse counterpart of STAT5 alpha is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this protein in cells. (fishersci.com)
  • Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. (bireme.br)
  • The protein encoded by this gene belongs to the ETS family of transcription factors. (wikipedia.org)
  • The messenger RNA and protein levels of DNA repair protein PARP1 are controlled, in part, by the expression level of the ETS1 transcription factor which interacts with multiple ETS1 binding sites in the promoter region of PARP1. (wikipedia.org)
  • We have investigated the activity of a mammary gland-specific transcription factor (MGF), which mediates hormonal influences at the level of a milk protein gene promoter. (semanticscholar.org)
  • The dual role of LSD1 and HDAC3 in STAT5-dependent transcription is determined by protein interactions, binding affinities, motifs and genomic posi. (nih.gov)
  • Our study describes an interaction network of STAT5a/LSD1/HDAC3 and a dual function of LSD1/HDAC3 on STAT5-dependent transcription, defined by protein-protein interactions, genomic binding localization/affinity and motifs. (nih.gov)
  • The transcription factors associated with STAT3 are c-Jun and cyclic AMP-responsive enhancer binding protein (CREB). (acris-antibodies.com)
  • protein phosphatase magnesium-dependent 1D) have a delay in HER2/neu (human epidermal growth factor 2), but not Wnt1-induced mammary tumor formation. (nih.gov)
  • In response to cytokines that signal through the common gamma chain such as IL-2, IL-7, and IL-15, STAT5 is phosphorylated on tyrosine 694 by JAK1 and JAK3. (fishersci.com)
  • The finding is important since agents that inhibit the Stat5 pathway are currently entering clinical trials, says the study's senior author, Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology, and Urology at Jefferson. (innovations-report.com)
  • We show that the new signal interceptors targeting the JAK-STAT5 pathway may have dangerous side effects that must be taken into account in clinical trials: inhibiting JAK-STAT5 has the potential to promote tumor growth by enhancing NK-cell-mediated angiogenesis. (aacrjournals.org)
  • pii: S1574-7891 (16) : 30001-1 IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma. (genetex.com)
  • Together, these bind to the STAT5-binding site in the promoter of bcl-X L . Overexpression of constitutively active STAT5 protected oligodendrocytes from apoptosis, and knockdown of STAT5 blocked the protective effects of MP, demonstrating the importance of STAT5 in this pathway. (jneurosci.org)
  • STAT5 subsequently dimerizes, translocates into the nucleus, and induces transcription. (ahajournals.org)
  • We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. (nature.com)
  • Experiments in cell culture and in mice showed that increased Stat5 copy numbers conferred a growth advantage for tumors. (innovations-report.com)
  • Stat5-deficient (Stat5KO) mice, although born with normal MC numbers, are completely MC deficient by 12 wk of age, due to lack of proper survival signals (Ref. 10 and C. Shelburne and J. Ryan, unpublished observations). (jimmunol.org)
  • We show that STAT5 normally represses the transcription of VEGFA in NK cells, in both mice and humans. (aacrjournals.org)
  • however, STAT5 alpha deficient female mice failed to lactate due to impairment of mammary development. (acris-antibodies.com)
  • Using traditional and cell-specific gene knock-out mice, researchers in LGP have discovered that STAT5 is essential for the development and function of several distinct cell types, including the mammary gland and liver. (nih.gov)
  • The overexpression of STAT5 has been shown to increase mammary carcinogenesis ( 13 ). (aacrjournals.org)
  • We now report that STAT5-deficient NK cells can be rescued by overexpression of BCL2. (aacrjournals.org)
  • 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)
  • We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. (aacrjournals.org)
  • Therefore, it was hypothesized that LPS would down-regulate mouse Oatp4 and that this action is due to a decrease in nuclear binding activity of one or more liver-enriched transcription factors to mouse Oatp4 promoter. (aspetjournals.org)
  • To date, one of our notable observations is that STAT5 can regulate fat cell development both in vitro and in vivo. (pbrc.edu)
  • These conditions are frequently caused by mutations that over-activate intracellular signalling or gene transcription. (vetmeduni.ac.at)
  • Some but not all of these NFI isoforms synergistically activate WAP gene transcription in cooperation with GR and STAT5, as determined using transient cotransfection assays in JEG-3 cells. (asm.org)
  • The CGCG boxes are gene transcription factors (TF). (wikiversity.org)
  • The GA responsive complexes are gene transcription factors (TF), notably the TAACAAA box or GA responsive element (GARE), the pyrimidine box CCTTTT, and the TATCCAC box (Skriver et al. (wikiversity.org)
  • STAT5 was also activated in primary mouse bone marrow cells acutely transformed by the CML-specific BCR-ABL oncogene, but not by the serine kinase oncogene v-MOS. (nih.gov)
  • In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death of colonic epithelial cells, induced by live E. histolytica trophozoites. (parasitol.kr)
  • Cotransfection experiments in Kit225 T cells resulted in cooperative transcriptional activity between both transcription factors in response to a combination of IL-2, PMA and ionomycin. (archives-ouvertes.fr)
  • Two of the three Stat5-presenting non-contiguous locations, one of which binds SHP-1 also, inhibited growth of Ba/F3 cells substantially. (researchreportone.com)
  • We know that Stat5 is absolutely critical to the survival of prostate cancer cells," she says. (innovations-report.com)
  • In 2010, Dr. Nevalainen found that excess Stat5 in prostate cancer cells is linked to metastasis, and excess Stat5 expression predicts early disease recurrence and death from prostate cancer. (innovations-report.com)
  • IL-2 and/or IL-15 can restore impaired CD56 NK cells, together with increased p-STAT5, which can be reversed by CD122 blockade. (bireme.br)
  • Differentiation of B cells into antibody-secreting cells (ASCs), plasmablasts and plasma cells is regulated by a network of transcription factors. (bireme.br)
  • Although NK cells are generally responsible for killing tumor cells, the rescued STAT5-deficient NK cells promote tumor formation by producing enhanced levels of the angiogenic factor VEGFA. (aacrjournals.org)
  • EPO-induced STAT5-dependent reporter gene expression was absent in Nox2-deficient cells. (ahajournals.org)
  • The rice WRKY transcription factor OsWRKY71 may be a transcriptional repressor in rice aleurone cells. (wikiversity.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)
  • CD4+ helper T cells are important producers of a range of such cytokines, and it is through the production of these factors that they orchestrate immune responses to eliminate a range of microbial pathogens. (nih.gov)
  • We discovered that both factors are required for the development of Bcr-Abl, but once established only Stat5 is crucial for the survival and growth of leukemic Cells," said Sexl. (thaindian.com)
  • Even mutated forms of bcr-abl, Leukaemia cells, which are resistant to inhibiting drugs such as Imatinib, are still dependent on Stat5. (thaindian.com)
  • In this study we demonstrated that bcr-abl, Leukaemia cells are addicted to Stat5 to maintain the leukameic state. (thaindian.com)
  • 2009). Using large scale genomic and genome-wide transcription factor binding and gene expression profiling LGP scientists continue to explore the chromatin landscape of mammary stem and cells throughout mammary development (Yamaji et al. (nih.gov)
  • however, STAT5 cannot engage DNA due to the condensed nature of chromatin in these cells. (furman.edu)
  • Presence of ASCs 1 ) enhanced interleukin (IL)-17A secretion by Th17 cells, 2 ) inhibited γ-interferon and tumor necrosis factor α secretion by Th1 cells, and 3 ) increased monocyte-mediated IL-1β secretion. (diabetesjournals.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)
  • IHC-P analysis of human lung carcinoma tissue using GTX37534 STAT5 antibody. (genetex.com)
  • We developed a tumours-specific gene-deletion approach to analyse the roles of Stat5 and Stat3 in Bcr/Abl-induced leukaemia growth. (thaindian.com)
  • The research team, based at Vetmeduni, Vienna, has been studying the STAT5 transcription factor, which is essential for the development of BCR/ABL-induced leukaemia. (b-s-h.org.uk)
  • These studies have also identified micro RNAs that are controlled during mammary development by STAT5. (nih.gov)
  • Developmental and environmental regulation of a mammary gland-specific nuclear factor essential for transcription of the gene encoding beta-casein. (semanticscholar.org)
  • STAT5 interacts with other factors to control transcription, and the mechanism of regulation is of interest as constitutive active STAT5 has been reported in malignancies. (nih.gov)
  • The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. (aacrjournals.org)
  • The degree to which the ETS1 transcription factor can bind to its binding sites on the PARP1 promoter depends on the methylation status of the CpG islands in the ETS1 binding sites in the PARP1 promoter. (wikipedia.org)
  • Their sequences and positions in the RAmy1A promoter (referred to the transcription initiation site) are indicated. (wikiversity.org)
  • Whereas the importance of STAT5 as tumor promoter is beyond doubt, the role of STAT3 in hematological cancers is less well understood. (mdpi.com)
  • I cloned these two Stat5 present in medaka, produced constitutive active and dominant negative gene versions and successfully established transgenic lines carrying each version under the control of the MITF promoter. (uni-wuerzburg.de)
  • Hypoxia is a common microenvironmental factor of solid tumors, promoting tumor growth as well as angiogenesis, metastasis, and therapy resistance [3] , [4] . (plos.org)
  • Coimmunoprecipitation experiments evidenced that a Stat5/Ets-1/2 complex is formed in vivo in absence of DNA. (archives-ouvertes.fr)
  • Stat5KO MC can be derived in vitro, where they develop and expand normally if maintained in IL-3 plus stem cell factor (SCF), conditions that do not appear to exist in vivo. (jimmunol.org)
  • To gain new in vivo information on candidate factors known to be involved in melanoma progression, I identified and analysed BRAF, Stat5 and C-myc in the laboratory fish model system medaka. (uni-wuerzburg.de)
  • In interferon resistant melanoma cell lines we found a high expression of STAT5 and a low expression of STAT1. (uni-heidelberg.de)
  • STAT1 is known to associate with the transcription factors p48, Sp1, and p300. (acris-antibodies.com)
  • Ets1 directly interacts with various transcription factors. (wikipedia.org)
  • When Ets1 interacts with other transcription factors (Runx1, Pax5, TFE3, and USF1) its final effect on transcription depends on whether C-terminal domain is phosphorylated. (wikipedia.org)
  • Functions as a transcriptional coactivator for STAT5. (uniprot.org)
  • To further our understanding how PLC-3 works its growth-suppressive function, we tried to finely map the Stat5- and SHP-1-presenting sites within PLC-3-CT (residues 809C1234). (researchreportone.com)
  • However, little is known about the role of STAT5 in solid tumours in general and its function in melanoma in particular. (nih.gov)
  • In 2004, Dr. Nevalainen found that Stat5 inside a cell's nucleus is often over-expressed in high-grade human prostate cancer, and in 2005, she demonstrated that Stat5 activity was associated with recurrence of prostate cancer in patients who had already been treated. (innovations-report.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)
  • Outcomes non-contiguous multiple brief peptides within PLC-3-CT content to Stat5 and SHP-1 Our prior research demonstrated that PLC-3-CT provides the growth suppressor function and includes the connections sites for Stat5 and SHP-1 [16]. (researchreportone.com)
  • These findings reveal that STAT5-directed therapies may have negative effects: In addition to impairing NK-cell-mediated tumor surveillance, they may even promote tumor growth by enhancing angiogenesis. (aacrjournals.org)
  • STAT5 alpha is critically involved in a variety of physiological functions, including reproduction, lactation, immune function and somatic growth. (thermofisher.com)
  • Basically it's the same with your liver and insulin-like growth factor 1. (nutritionfacts.org)
  • In this stem cell from bone marrow are injected into a recipient after treating them with growth factor. (medindia.net)
  • Stat5 is a transcription factor known to be constitutively activated in fish melanoma. (uni-wuerzburg.de)
  • Within this network, factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. (bireme.br)
  • These results suggest that celecoxib promotes hepatocyte differentiation of hiHep by activating STAT5 and is useful for the generation of functional hiHep. (aspetjournals.org)
  • These data provide key insights into how IL-2 promotes T cell function and highlight signaling mechanisms and transcription factors that integrate oxygen sensing to transcriptional control of CD8 T cell differentiation. (babraham.ac.uk)
  • 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)
  • Given the critical role for Stat5 in survival, we questioned whether this transcription factor also might play a role in MC function. (jimmunol.org)
  • However, differential accumulation of STAT5 alpha and STAT5 beta mRNA has been reported for both muscle and mammary tissue. (fishersci.com)
  • Moreover, the increase in CYP3A4 mRNA expression was attenuated by cotreatment with STAT5 inhibitor. (aspetjournals.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)
  • This work demonstrates a key role of the B lymphocyte transcription factor BCL11A in dendritic cell (DC) development. (pnas.org)
  • The role of Stat5 transcription factors as tumor suppressors or oncogenes. (semanticscholar.org)
  • Here we show that the transcription factor Kruppel-like factor 13 (KLF13) has a critical role in the HPV life cycle. (ovid.com)