A B7 antigen subtype that inhibits the costimulation of T-cell activation, proliferation, cytokine production and development of cytotoxicity. The over expression of this protein in a variety of tumor cell types suggests its role in TUMOR IMMUNE EVASION.
An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.
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.
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.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
An essential amino acid. It is often added to animal feed.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
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.
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.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
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.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
A genus of flexible, spiral rods found in hydrogen sulfide-containing mud, sewage, and polluted water. None of the species properly referred to in this genus are pathogenic.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
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.
Established cell cultures that have the potential to propagate indefinitely.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Glycoproteins found on the membrane or surface of cells.
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.
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
Antibodies produced by a single clone of cells.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
A genus of gram-negative gliding bacteria found in SOIL; HUMUS; and FRESHWATER and marine habitats.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
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.
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 encapsulated lymphatic organ through which venous blood filters.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.
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.
The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Substances that are recognized by the immune system and induce an immune reaction.
Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Proteins prepared by recombinant DNA technology.
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.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
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.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
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.
Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
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.
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
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.
T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
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.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
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 study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The number of LYMPHOCYTES per unit volume of BLOOD.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
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 biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.
Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).
A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
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 ZINC FINGER MOTIF containing immediate early protein that is closely related to TRISTETRAPROLIN. It interacts with and helps destabilize VASCULAR ENDOTHELIAL GROWTH FACTOR mRNA.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
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.
Sites on an antigen that interact with specific antibodies.
An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Elements of limited time intervals, contributing to particular results or situations.
The rate dynamics in chemical or physical systems.
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.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)
A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
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.
Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.
Reduction in the number of lymphocytes.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
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.
The major group of transplantation antigens in the mouse.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A quiescent state of cells during G1 PHASE.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A multisubunit polycomb protein complex with affinity for CHROMATIN that contains methylated HISTONE H3. It contains an E3 ubiquitin ligase activity that is specific for HISTONE H2A and works in conjunction with POLYCOMB REPRESSIVE COMPLEX 2 to effect EPIGENETIC REPRESSION.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
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.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
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.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
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.
The relationships of groups of organisms as reflected by their genetic makeup.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
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 basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Adherence of cells to surfaces or to other cells.
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.

B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. (1/43)

We identify a B7 family molecule, B7-H4, by protein sequence analysis and comparative molecular modeling. While B7-H4 mRNA is widely distributed in mouse and human peripheral tissues, cell surface expression of B7-H4 protein is limited and shows an inducible pattern on hematopoietic cells. Putative receptor of B7-H4 can be upregulated on activated T cells. By arresting cell cycle, B7-H4 ligation of T cells has a profound inhibitory effect on the growth, cytokine secretion, and development of cytotoxicity. Administration of B7-H4Ig into mice impairs antigen-specific T cell responses whereas blockade of endogenous B7-H4 by specific monoclonal antibody promotes T cell responses. B7-H4 thus may participate in negative regulation of cell-mediated immunity in peripheral tissues.  (+info)

B7S1, a novel B7 family member that negatively regulates T cell activation. (2/43)

T cell activation by antigen-presenting cells (APC) is regulated by positive and negative costimulatory molecules in the B7 family. Here we describe a novel addition in this family, designated as B7S1, which is uniquely anchored to the cell membrane via a GPI linkage. B7S1 is expressed on professional APC and widely distributed in nonlymphoid tissues. A soluble B7S1-Ig fusion protein binds to activated but not naive T cells. B7S1-Ig inhibits T cell activation and IL-2 production. A monoclonal antibody that blocks binding of B7S1 to its receptor enhances T cell proliferation in vitro and exacerbates experimental autoimmune encephalomyelitis in vivo. This study identifies a novel negative regulator of T cell activation and further reveals complex costimulatory regulation of immune responses.  (+info)

Regulatory roles of IL-2 and IL-4 in H4/inducible costimulator expression on activated CD4+ T cells during Th cell development. (3/43)

We found a tight correlation among the levels of H4/inducible costimulator (ICOS) expression, IL-4 production, and GATA-3 induction, using activated CD4(+) T cells obtained from six different murine strains. BALB/c-activated CD4(+) T cells expressed approximately 10-fold more H4/ICOS on their surfaces and produced approximately 10-fold more IL-4 upon restimulation than C57BL/6-activated CD4(+) T cells. BALB/c naive CD4(+) T cells were shown to produce much higher amounts of IL-2 and IL-4 upon primary stimulation than C57BL/6 naive CD4(+) T cells. Neutralization of IL-4 with mAbs in culture of BALB/c naive CD4(+) T cells strongly down-regulated both H4/ICOS expression on activated CD4(+) T cells and IL-4 production upon subsequent restimulation. Conversely, exogenous IL-4 added to the culture of BALB/c or C57BL/6 naive CD4(+) T cells up-regulated H4/ICOS expression and IL-4 production upon restimulation. In addition, retroviral expression of GATA-3 during the stimulation of naive CD4(+) T cells from C57BL/6 or IL-4(-/-) mice increased H4/ICOS expression on activated CD4(+) T cells. A similar effect of IL-2 in the primary culture of BALB/c naive CD4(+) T cells appeared to be mediated by IL-4, the production of which was regulated by IL-2. These data suggest that IL-4 induced by IL-2 is critical to the maintenance of high H4/ICOS expression on BALB/c-activated CD4(+) T cells.  (+info)

Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. (4/43)

B7-H4 is a recently identified B7 family member that negatively regulates T cell immunity by the inhibition of T cell proliferation, cytokine production, and cell cycle progression. In this study, we report that the genomic DNA of human B7-H4 is mapped on chromosome 1 comprised of six exons and five introns spanning 66 kb, of which exon 6 is used for alternative splicing to generate two different transcripts. Similar B7-H4 structure is also found in mouse genomic DNA in chromosome 3. A human B7-H4 pseudogene is identified in chromosome 20p11.1 with a single exon and two stop codons in the coding region. Immunohistochemistry analysis using B7-H4-specific mAb demonstrates that B7-H4 is not expressed on the majority of normal human tissues. In contrast, up to 85% (22 of 26) of ovarian cancer and 31% (5 of 16) of lung cancer tissues constitutively express B7-H4. Our results indicate a tight regulation of B7-H4 expression in the translational level in normal peripheral tissues and a potential role of B7-H4 in the evasion of tumor immunity.  (+info)

B7-h4 is highly expressed in ductal and lobular breast cancer. (5/43)

PURPOSE: This study was designed to investigate the expression of B7-H4 protein, a member of the B7 family that is involved in the regulation of antigen-specific immune responses, in normal breast and in primary and metastatic breast carcinomas. EXPERIMENTAL DESIGN: Archival formalin-fixed tissue blocks from breast cancers and normal somatic tissues were evaluated for B7-H4 expression by immunohistochemistry with manual and automated image analysis. The proportion of B7-H4-positive cells and the intensity of B7-H4 staining were compared with histologic type, grade, stage, hormone receptor status, and HER-2/neu status. RESULTS: B7-H4 was detected in 165 of 173 (95.4%) primary breast cancers and in 240 of 246 (97.6%) metastatic breast cancers. B7-H4 staining intensity was greater in invasive ductal carcinomas [24.61 relative units (RU)] and in invasive lobular carcinomas (15.23 RU) than in normal breast epithelium (4.30 RU, P = 0.0003). Increased staining intensity was associated with negative progesterone receptor status (P = 0.014) and history of neoadjuvant chemotherapy (P = 0.004), and the proportion of B7-H4-positive cells was associated with negative progesterone receptor (P = 0.001) and negative HER-2/neu (P = 0.024) status. However, there was no statistically significant relationship between the proportion of B7-H4-positive cells or staining intensity and grade, stage, or other clinicopathologic variables. Low levels of B7-H4 expression were also detected in epithelial cells of the female genital tract, lung, pancreas, and kidney, but B7-H4 was generally absent in most other normal somatic tissues. CONCLUSIONS: The nearly ubiquitous expression of B7-H4 in breast cancer, independent of tumor grade or stage, suggests a critical role for this protein in breast cancer biology.  (+info)

B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. (6/43)

Using cDNA database mining strategies and real-time quantitative reverse transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in ovarian and breast cancer tissues when compared with normal tissues. The gene encodes a protein of 282 amino acids with a signal sequence, an immunoglobulin domain, and a COOH-terminal hydrophobic transmembrane domain. Immunohistochemistry experiments show plasma membrane staining in serous ovarian and breast cancer, confirming the tissue specificity and cell surface localization. We have developed a sensitive dual monoclonal antibody sandwich ELISA to analyze the level of B7-H4 protein in >2,500 serum samples, ascites fluids, and tissue lysates. High levels of B7-H4 protein were detected in ovarian cancer tissue lysates when compared with normal tissues. B7-H4 was present at low levels in all sera but showed an elevated level in serum samples from ovarian cancer patients when compared with healthy controls or women with benign gynecologic diseases. The median B7-H4 concentration in endometrioid and serous histotypes was higher than in mucinous histotypes, consistent with results of immunohistochemical staining. The multivariate logistic regression analysis of B7-H4 and CA125 measured in the same sample set resulted in an area under the curve (AUC) of 0.86 for all stages and 0.86 for stage I/II patients, which was significantly higher than the AUC for either marker alone. In early-stage patients, the sensitivity at 97% specificity increased from 52% for CA125 alone to 65% when used in combination with B7-H4. We conclude that B7-H4 is a promising new biomarker for ovarian carcinoma.  (+info)

B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. (7/43)

Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.  (+info)

Recombinant human B7-H4 expressed in Escherichia coli inhibits T lymphocyte proliferation and IL-2 secretion in vitro. (8/43)

AIM: To explore the biofunctions of human B7-H4 generated from prokaryotic system. METHODS: The gene of human B7-H4 extracellular region (IgV-like and IgC-like domains) was obtained by PCR from human cDNA FLJ22418 and then inserted into the prokaryotic expression vector pGEX-5X-3 expressing glutathione s-transferase (GST) fusion protein. After being identified by restriction enzyme digestion and sequencing, the recombinant vector was transferred into host strain E coli BL21-RIL(DE3). A 47 kDa fusion protein (GST/hB7-H4) was induced by isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified by standard methods reported in the prokaryotic system. The inhibitory effect of GST/hB7-H4 on proliferation of T cells was observed in vitro by CD3mAb activated T-cell culturing system and [(3)H]-thymidine incorporation assay. The concentrations of interleukin-2 and iterferon-g in the supernatants of T cells were determined by ELISA. RESULTS: We successfully constructed the method for high-level expression and purification of the hB7-H4 extracellular domain as GST fusion protein from E coli. The GST/hB7-H4 fusion protein produced in bacteria had obvious biological activity to inhibit T-lymphocyte proliferation and IL-2 secretion. CONCLUSION: The prokaryote expression system could be used to generate hB7-H4 protein with natural spatial conformations and biological functions, which provided an efficient and economical way for the preparation of this target protein.  (+info)

V-set domain-containing T-cell activation inhibitor 1 is a protein that in humans is encoded by the VTCN1 gene. B7H4 belongs to the B7 family (see CD80; MIM 112203) of costimulatory proteins. These proteins are expressed on the surface of antigen-presenting cells and interact with ligands (e.g., CD28; MIM 186760) on T lymphocytes.[supplied by OMIM] B7-H4 is an immune checkpoint molecule. B7 (protein) GRCh38: Ensembl release 89: ENSG00000134258 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000051076 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L (June 2003). B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 18 (6): 849-61. doi:10.1016/S1074-7613(03)00152-3. PMID 12818165. Prasad DV, Richards S, Mai XM, Dong C (June 2003). B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity. 18 (6): 863-73. ...
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Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression
Cancer immunotherapies such as drugs targeting the immune inhibitory molecules known as PD-1 and PD-L1 have shown benefit across a number of cancers.
Mouse monoclonal antibody raised against full length recombinant human B3GAT1. Recombinant protein corresponding to full length human B3GAT1. (MAB13284) - Products - Abnova
JSH-23 is a nuclear factor-kappa B (NF-κB) nuclear translocation inhibitor. JSH-23 inhibits LPS and cytokine-induced nuclear translocation of the p65 subunit of NF-kB as analyzed by EMSA and western blot. JSH-23 treatment significantly reversed the nerve conduction and nerve blood flow deficits seen in diabetic animals. Reduction in mechanical pain threshold was also partially corrected by the treatment. Protein expression studies showed that nuclear translocation of p65/p50 subunit was inhibited by JSH-23 treatment in the sciatic nerve..
VSIG10L2 (V-set and immunoglobulin domain containing 10 like 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Persistently hyperphosphorylated Akt contributes to human oncogenesis and resistance to therapy. Triciribine (TCN) phosphate (TCN-P), the active metabolite of the Akt phosphorylation inhibitor TCN, is in clinical trials, but the mechanism by which TCN-P inhibits Akt phosphorylation is unknown. Here we show that in vitro, TCN-P inhibits neither Akt activity nor the phosphorylation of Akt S473 and T308 by mammalian target of rapamycin or phosphoinositide-dependent kinase 1. However, in intact cells, TCN inhibits EGF-stimulated Akt recruitment to the plasma membrane and phosphorylation of Akt. Surface plasmon resonance shows that TCN, but not TCN, binds Akt-derived pleckstrin homology (PH) domain (K(D) 690 nM). Furthermore, nuclear magnetic resonance spectroscopy shows that TCN-P, but not TCN, binds to the PH domain in the vicinity of the PIP3-binding pocket. Finally, constitutively active Akt mutants, Akt1-T308D/S473D and myr-Akt1, but not the transforming mutant Akt1-E17K, are resistant to TCN ...
Objective: Endogenous expression of apoE has a significant impact on adipocyte lipid metabolism and is markedly suppressed in obesity. Adipose tissue oxidant stress is emerging as an important mediator of adipocyte dysfunction. These studies were undertaken to evaluate the role of oxidant stress for regulation of adipocyte apoE.. Research Design and Methods: ApoE gene and protein expression in 3T3-L1 adipocytes, or mature adipocytes and adipose tissue from C57/Bl6 mice was evaluated after induction of oxidant stress. The response of adipose tissue and adipocytes from obese compared to lean mice to antioxidants was also assessed.. Results: Oxidant stress in 3T3-L1 cells, or adipocytes and adipose tissue from lean mice significantly reduced apoE mRNA and protein level. Inclusion of an antioxidant eliminated this reduction. Oxidant stress was accompanied by activation of the NF-κB transcription complex and its effect on apoE was eliminated by an NF-κB activation inhibitor. Treatment of freshly ...
Among high-risk patients undergoing CABG, the use of perioperative acadesine for 7 hours was not beneficial. This agent did not reduce all-cause mortality, nonfatal stroke, or need for mechanical support compared with placebo. This contrasts the results of five previous studies in over 4,000 patients, which suggested benefit with acadesine. This medication joins the list of other disproven cardioprotective drugs during CABG: sodium-proton exchange inhibitor, purinergic receptor antagonist, and complement activation inhibitor.. ...
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Were it possible for us today to catalog the reasons why Christians leave the faith, no doubt the list would be quite lengthy. Likely, however, included among those reasons would be some, or all, of the following.. First, some fall away because they neglect their own spiritual welfare. The Scriptures are clear regarding the fact that Christians have been provided a great salvation that should not be neglected (Hebrews 2:3). When a person does what the Bible commands him to do to be saved, he enters the kingdom (i.e., the church) as a newborn enters an earthly family-in need of milk for sustenance and tender care for survival. The apostle Peter spoke of such people as newborn babes who were to long for the spiritual milk which is without guile, that ye may grow thereby unto salvation (1 Peter 2:2). Paul discussed those whom he had fed spiritually with milk, not with meat because they were not yet ready for such (1 Corinthians 3:2). But just as the neonatal child eventually grows into ...
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Expression of the α-subunit of the amiloride-sensitive sodium channel (αENaC) is regulated by a number of factors in the lung, including oxygen partial pressure (Po2). As transcriptional activation is a mechanism for raising cellular mRNA levels, we investigated the effect of physiological changes in Po2 on the activity of the redox-sensitive transcription factor nuclear factor κB (NF-κB) and transcriptional activity of 5′-flanking regions of the human αENaC gene using luciferase reporter-gene vectors transiently transfected into human adult alveolar carcinoma A549 cells. By Western blotting we confirmed the presence of NF-κB p65 but not p50 in these cells. Transiently increasing Po2 from 23 to 42mmHg for 24h evoked a significant increase in NF-κB DNA-binding activity and transactivation of a NF-κB-driven luciferase construct (pGLNF-κBpro), which was blocked by the NF-κB activation inhibitor sulphasalazine (5mM). Transcriptional activity of αENaC-luciferase constructs containing ...
V-set domain-containing T-cell activation inhibitor 1 is a protein that in humans is encoded by the VTCN1 gene. B7H4 belongs to ... "Entrez Gene: VTCN1 V-set domain containing T cell activation inhibitor 1". Maruyama K, Sugano S (January 1994). "Oligo-capping ... Prasad DV, Richards S, Mai XM, Dong C (June 2003). "B7S1, a novel B7 family member that negatively regulates T cell activation ... a widely expressed B7 family member that inhibits T cell activation". Proceedings of the National Academy of Sciences of the ...
... which effectively reorganizes the actin cytoskeleton of the cell. In the case of neurons, activation of this pathway results in ... domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. As a transmembrane protein, it can mostly be found ... To be able to understand how these components regulate signalling processes an experiment has been set up "model of serum ... Known interactions are with proteins such as Oligodendrocyte-myelinn glycoprotein, Nogo-A (neurotic outgrowth inhibitor), and ...
HIF prolyl-hydroxylase has been targeted by a variety of inhibitors that aim to treat stroke, kidney disease, ischemia, anemia ... Clinically observed prolyl hydroxylase domain mutations, as in the case of erythrocytosis- and breast cancer-associated PHD2 ... Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond ... "Activation of the hypoxia-inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase ...
Activation of factor VIII to factor VIIIa is done by cleavage and release of the B domain. The protein is now divided to a ... Factor VIII is produced in liver sinusoidal cells and endothelial cells outside the liver throughout the body. This protein ... This interaction sets off a chain of additional chemical reactions that form a blood clot. Factor VIII participates in blood ... the incidence of these inhibitors is dependent of various factors, including the factor VIII product itself. In the 1980s, some ...
More importantly, each GluN2 subunit has a different intracellular C-terminal domain that can interact with different sets of ... produced by activation of an NMDA receptor increases the concentration of Ca2+ in the cell. The Ca2+ can in turn function as a ... NMDAR/TRPM4 interaction interface inhibitors (also known as ‚interface inhibitors') disrupt the NMDAR/TRPM4 complex and ... Granule cell precursors (GCPs) of the cerebellum, after undergoing symmetric cell division in the external granule-cell layer ( ...
They found unexpected patterns of brain activation in awake rats that were exposed to sodium butyrate, an HDAC inhibitor (or ... targeted gene activation, and behavioral adaptations to long-term cocaine exposure. The second set of experiments that Renthal ... Between exposure and 24 hours after, HDAC5 returns to the cell nucleus to limit the expression of these cocaine-regulated genes ... mutant proteins and HDAC inhibitors suggested that HDAC5's action is mediated through its catalytic histone deacetylase domain ...
Direct thrombin inhibitors provides an excellent example of negative allosteric modulation. Allosteric inhibitors of thrombin ... PFK can be allosterically inhibited by high levels of ATP within the cell. When ATP levels are high, ATP will bind to an ... The allostery landscape model introduced by Cuendet, Weinstein, and LeVine allows for the domains to have any number of states ... In this way, an allosteric ligand modulates the receptor's activation by its primary orthosteric ligand, and can be thought to ...
It is likely that, in animal cells, at least some of the activation of APC/CCdc20 occurs early in the cell cycle (prophase or ... These proteins target the APC/C to specific sets of substrates at different times in the cell cycle, thus driving it forward. ... The catalytic core of the APC/C consists of the cullin subunit Apc2 and RING H2 domain subunit Apc11. These two subunits ... i.e.: The subunit, CDC20 allows APC to degrade substrates such as anaphase inhibitors (Pdsp1) at the beginning of anaphase, on ...
Most CCPs prevent activation of the complement system on the surface of host cells and protect host tissues against damage ... RCA proteins typically possess CCP domains, also termed Sushi domains or Short Consensus Repeats (SCR). Such beta-sandwich ... Gialeli C, Gungor B, Blom AM (October 2018). "Novel potential inhibitors of complement system and their roles in complement ... factor B will bind and the cascade will be set off as normal. This mechanism of immune regulation using Factor H has been ...
It has two C2-set immunoglobulin domains, and it's probable that the binding site for its ligand is near the interdomain hinge ... Killer Activation Receptors (KARs) are receptors expressed on the plasmatic membrane of Natural Killer cells (NK cells). KARs ... is an inhibitor complex). It's important to mention that most KIRs have an inhibitor function, which has been generalized in ... In fact, these intracellular domains determine the opposite functions of activation and inhibitory receptors. Activation ...
... while repressors inhibit the cell cycle. Yet, both sets of E2F have similar domains. E2F1-6 have DP1,2 heterodimerization ... activation of E2F-3a genes follows upon the growth factor stimulation and the subsequent phosphorylation of the E2F inhibitor ... In REF52 cells, overexpression of activator E2F1 is able to push quiescent cells into S phase. While repressors E2F4 and 5 do ... In activators, E2F binding with pRB has been shown to mask the transactivation domain responsible for transcription activation ...
"Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to ... "Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell ... Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. It ... Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718. Collins FS ...
The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for ... activation domain binds to an allosteric site on the KIX domain". The Journal of Biological Chemistry. 277 (45): 43168-74. doi: ... "MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency". Cell Stem Cell. 18 (4): 481-94. doi:10.1016/j.stem. ... It has been proposed that the small molecule inhibitor MM-401, which was used to inhibit MLL1, changes the distribution of ...
AHR activation by FICZ can promote the development of Th17 cells causing inflammation and autoimmunity, but also promote an ... Furthermore, the expansion of human induced pluripotent stem cells (iPSC) was enhanced by the AHR inhibitor CH223191. In ... Lamas and co-workers showed that mice with dysbiotic microbiota due to their lack of the caspase recruitment domain 9 (CARD9) ... The effect of AhR ligands in reversing inflammatory responses was also demonstrated in a clinical setting. FICZ treatment of ...
The intracellular part is a global-like domain, known as a death domain, which consists of two sets of perpendicular helixes ... increased levels of CD271 were observed in brain metastatic melanoma cells whereas resistance to the BRAF inhibitor vemurafenib ... p75NTR c-Jun kinase pathway activation (which causes apoptosis) is suppressed when NGF binds to TrkA. p75NTR activation of NF- ... The extracellular domain consists of a stalk domain connecting the transmembrane domain and four cysteine-rich repeat domains, ...
Katoh H, Hiramoto K, Negishi M (January 2006). "Activation of Rac1 by RhoG regulates cell migration". Journal of Cell Science. ... via its GEFD1 domain) and also on RhoA via a separate GEF domain (GEFD2). Activation of RhoG by TRIO has been shown to promote ... Like most small G proteins RhoG is involved in a diverse set of cellular signalling mechanisms. In mammalian cells these ... A third group, known as Guanine nucleotide dissociation inhibitors (GDIs), inhibit dissociation of GDP and thus lock the G ...
This gene encodes SET domain containing 2, a protein that acts to reduce the occurrence of gene deletions and tumor formation. ... They also commonly express cytotoxic T cell activation markers such as TIA1, granzyme B, and perforin and therefore may have ... the CDKN2A gene which encodes cyclin-dependent kinase Inhibitor 2A, a protein that regulates cell proliferation and the CDKN2B ... particularly lymphoplasmacytoid cells, i.e. cells showing a mixture of B cell and plasma cell morphological features) or of ...
Earlier that year, another set of scientists had claimed to discover a new protein domain which they called a DHR domain. Dr. ... both play an important role at cell junctions and in cell signaling complexes. Since the discovery of PDZ domains more than 20 ... Different PDZ domains can even have this allosteric effect on each other. This PDZ-PDZ interaction only acts as an inhibitor. ... In the human brain, nitric oxide often acts in the synapse to modify cGMP levels in response to NMDA receptor activation. In ...
This domain is different from the α-ACB domain of eubacteria; it shares strong homology with the C-terminal domain of the ... native YARS has no cell-signaling activity, the enzyme is secreted during apoptosis in cell culture and can be cleaved with an ... However, kinetic studies of tyrosine activation and tRNA(Tyr) charging have revealed an anticooperative behavior of the TyrRS ... "Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors". ...
... and an H3K9me2 methyltransferase SET domain bifurcated 1 (SETDB1) were also implicated in diabetes related adipogenesis. The ... When IRX3 was knocked out, there was a drop in the number of β-cells that produce insulin and the α-cells that produce glucagon ... The role of other HDACs and the potential use of HDAC inhibitors in diabetes is not very clear. Other treatments look towards ... SIRT1 overexpression or activation by resveratrol could improve insulin resistance and SIRT1 activators are being developed for ...
This constant activation is brought about either by mutations or by aberrant expressions of cell signalling, resulting in poor ... "Small molecule STAT5-SH2 domain inhibitors exhibit potent antileukemia activity". J. Med. Chem. 55 (3): 1047-55. doi:10.1021/ ... Once in the nucleus, the dimers bind to STAT5 response elements, inducing transcription of specific sets of genes. Upregulation ... or cell proliferation programmed cell death, or apoptosis cell specialization, or differentiation and inflammation. Activated ...
However, plants do not have circulating immune cells, so most cell types exhibit a broad suite of antimicrobial defenses. ... The E3 enzyme components can be grouped by which domains they contain and include several types. These include the Ring and U- ... R gene products control a broad set of disease resistance responses whose induction is often sufficient to stop further ... These events in turn typically lead to the modification of proteins that control gene transcription, and the activation of ...
Selenate induces epithelial-mesenchymal transition in a colorectal carcinoma cell line by AKT activation. Experimental Cell ... Inhibitors of de novo ceramide synthesis seem to prevent PP1 activation (Ghosh et al., 2007). The effects of ceramide on ... I2PP2A has also been identified as a truncated SET protein (Janssens & Goris, 2001). SET proteins, such as I2PP2A have been ... I1PP2A and I2PP2A inhibit all possible forms of CAPP by associating with the catalytic subunit using their C-terminal domains ( ...
There is a human ortholog to mouse Set protein (phosphatase 2A inhibitor or I2PP2A), and it is localized to the nucleus. Set ... C14orf93 is part of the family DUF4616; this family is marked by a domain of unknown function in the C-terminal domain. DUF4616 ... There is markedly higher expression seen in T cells, and there is a slightly higher expression pattern shown in other immune ... which may serve as sites of activation or deactivation. N-acetylation is predicated at the second residue; this modification ...
The structure of the complex of SMAD3 and SMAD4 MH2 domains has been determined. The MH2 fold is defined by two sets of ... cancer is related with the regulation of angiogenic molecules expression in tumor vascularization and cell-cycle inhibitor in ... Smad3 activation plays a role in the pathogenesis of renal fibrosis, probably by inducing activation of bone marrow-derived ... Shi, Yigong; Massagué, Joan (2003). "Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus". Cell. 113 (6): 685-700. ...
Purine synthesis inhibitors inhibit the proliferation of cells, especially leukocytes. These inhibitors include azathioprine, ... A nearly complete, or complete, set of genes required for purine biosynthesis was determined to be present in 58 of the 65 ... Organisms in all three domains of life, eukaryotes, bacteria and archaea, are able to carry out de novo biosynthesis of purines ... concentration binds the enzyme to exerts inhibition while PRPP is in large amount binds to the enzyme which causes activation. ...
... s act as tumor inhibitors by preventing cellular proliferation of tumor cell lines. For example, in the epithelial- ... The transmembrane domains contain an unusual alanine/glycine sequence motif, while the cytoplasmic domain is essentially ... First is growth-factor-receptor activation. Glycosaminoglycans attached to the syndecan help binding of the various growth ... are an important component of syndecan and are responsible for a diverse set of syndecan functions. The addition of ...
Direct thrombin inhibitors provides an excellent example of negative allosteric modulation. Allosteric inhibitors of thrombin ... Bu Z, Callaway DJ (2011). Proteins move! Protein dynamics and long-range allostery in cell signaling. Advances in Protein ... The allostery landscape model introduced by Cuendet, Weinstein, and LeVine[5] allows for the domains to have any number of ... In this way, an allosteric ligand modulates the receptor's activation by its primary orthosteric ligand, and can be thought to ...
Alofanib is a novel first-in-class allosteric small-molecular inhibitor of FGFR2. It binds to the extracellular domain of FGFR2 ... Lee KM, Santos-Ruiz L, Ferretti P (Mar 2010). "A single-point mutation in FGFR2 affects cell cycle and Tgfbeta signalling in ... The first is associated with constitutive activation of FGFR, where the FGFR2 receptor is always signalling, regardless of the ... The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream ...
ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume ... The intracellular domain maintains two consensus catalytic domains for guanylyl cyclase activity. Binding of a natriuretic ... Several inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Most of ... ANP binds to a specific set of receptors - ANP receptors. Receptor-agonist binding causes the increase in renal sodium ...
... a novel potent inhibitor of signal transduction and growth in vitro and in vivo in small cell lung cancer cells". Cancer ... Their activation stimulates the vomiting reflex. Different emetic pathways exist, and substance P/NK1R appears to be within the ... even if through vagal terminals in the clinical setting. ... pathway of substance P and its seven-transmembrane domain NK1 ... Substance P has been known to stimulate cell growth in normal and cancer cell line cultures,[37] and it was shown that ...
5α-Reductase inhibitorsEdit. 5α-Reductase inhibitors such as finasteride and dutasteride are inhibitors of 5α-reductase, an ... N-Terminal domain antagonistsEdit. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all currently ... Cell Biol. 42 (6): 813-27. doi:10.1016/j.biocel.2009.11.013. PMID 19931639.. ... induced release of gonadotropins and consequent activation of gonadal androgen production.[2][64] Examples include GnRH ...
regulation of protein localization to cell surface. • regulation of receptor activity. • activation of phospholipase C activity ... NMDA receptor activation triggers the release of the regulatory inhibitor, allowing for BDNF exon IV upregulation to take place ... BDNF signaling leads to the autophosphorylation of the intracellular domain of the TrkB receptor (ICD-TrkB). Upon ... http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537∫:_Set_key=847156 ...
positive regulation of heterotypic cell-cell adhesion. • negative regulation of mitotic cell cycle. • endothelial cell ... Activation of the MAPK pathways: Of the three major MAPK cascades, TNF induces a strong activation of the stress-related JNK ... This dissociation enables the adaptor protein TRADD to bind to the death domain, serving as a platform for subsequent protein ... These disorders are sometimes treated by using a TNF inhibitor. This inhibition can be achieved with a monoclonal antibody such ...
Vorinostat is a second generation inhibitor that is fairly non-toxic and found to be effective in cell culture at low ... ERG-associated protein with SET domain (ESET)), which targets and trimethylates H3-K9 residues.[82] It's proposed that this ... Epigenetic treatment through SMN2 gene activation[edit]. Although SMA is not caused by an epigenetic mechanism, therapeutic ... HDAC inhibitor (small molecule) benzamide M344 MC 19 fatty acid Sodium butyrate M (y) 5, 6, 7 ; H (ny) D (y) 11 M (y) 14; R (y ...
regulation of protein localization to cell surface. • regulation of receptor activity. • activation of phospholipase C activity ... Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions ... BDNF signaling leads to the autophosphorylation of the intracellular domain of the TrkB receptor (ICD-TrkB). Upon ... http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537∫:_Set_key=847156 ...
"SET domain proteins modulate chromatin domains in eu- and heterochromatin". Cell. Mol. Life Sci. 54 (1): 80-93. PMID 9487389. ... "The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells.". Stem Cells Dev. 22: 654 ... Epigenetic changes modify the activation of certain genes, but not the genetic code sequence of DNA. The microstructure (not ... Costa S, Shaw P (March 2007). "'Open minded' cells: how cells can change fate" (PDF). Trends Cell Biol. 17 (3): 101-6. PMID ...
Noncatalytic domains[edit]. The novel domain additions to aaRS genes are accretive and progressive up the Tree of Life.[18][19] ... Molecular Cell Biology. 11 (9): 668-74. doi:10.1038/nrm2956. PMC 3042954. PMID 20700144.. ... A general structure of an aminoacyl-tRNA synthetase is shown here with an editing site as well as an activation site. The main ... "Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs". Nature. 347 (6289): 203-6 ...
... number of sets of chromosomes in the cell, and specific genetic abnormalities, such as translocations. Hyperdiploid cells are ... Recently, there has also been evidence and approval of use for dasatinib, a tyrosine kinase inhibitor. It has shown efficacy in ... and the intracellular domain of CD3-zeta containing ITAM repeats. Other sequences frequently included are: 4-1bb and OX40.[52] ... "The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures". Leukemia. 25 (1): ...
... is also described as selective ALOX5 inhibitor effective in a range of cell-free and cell-based model systems.[49] In addition ... A PLAT domain within its C2-like domain; this domain, by analogy to other PLAT domain-bearing proteins, may serve as a mobile ... The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular ... are known to regulate ALOX5 activity in vitro but have not been fully integrated into its physiological activation during cell ...
... after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke.[140][141] Endothelial cells lining ... The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit in the United States of ... McCarty MF, Block KI (September 2006). "Preadministration of high-dose salicylates, suppressors of NF-kappaB activation, may ... it was too late in the autumn of 1915 to reclaim the word which had already passed into the public domain. If the consuming ...
Oxamate is a cytosolic inhibitor of LDH A that significantly decreases ATP production in tumorous cells as well as increasing ... This article incorporates text from the public domain Pfam and InterPro IPR015409 ... Elevated LDH in the setting of upper respiratory symptoms in an HIV patient suggests, but is not diagnostic for, PCP. However, ... These ROS drive cancer cell proliferation by activating kinases that drive cell cycle progression growth factors at low ...
In MDR-expressing cells, the addition of an MDR inhibitor or an MDR substrate in excess dramatically increases the rate of ... The TM domains are categorized into three distinct sets of folds: type I ABC importer, type II ABC importer and ABC exporter ... For instance, a potential lethal increase in osmotic strength is counterbalanced by activation of osmosensing ABC transporters ... These domains consist of two trans-membrane (T) domains and two cytosolic (A) domains. The two T domains alternate between an ...
Direct thrombin inhibitors provides an excellent example of negative allosteric modulation. Allosteric inhibitors of thrombin ... PFK can be allosterically inhibited by high levels of ATP within the cell. When ATP levels are high, ATP will bind to an ... The allostery landscape model introduced by Cuendet, Weinstein, and LeVine [8] allows for the domains to have any number of ... Positive allosteric modulation (also known as allosteric activation) occurs when the binding of one ligand enhances the ...
... which can give rise to fat cells, bone cells as well as other cell types. The fact that MAT increases in the setting of calorie ... BAT activation may also occur in response to overfeeding.[47] UCP1 activity is stimulated by long chain fatty acids that are ... PR domain containing 16 (PRDM16),[59] peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and Early ... of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue ...
BmN4 cells). This system uses the GAL4 BD and the activation domain of mouse NF-κB P65. Both are under the control of the OpIE2 ... In this set up the bait and prey harboring cells are mated in a random order. After mating and selecting surviving cells on ... "The fluorescent two-hybrid assay to screen for protein-protein interaction inhibitors in live cells: targeting the interaction ... The BD is the domain responsible for binding to the UAS and the AD is the domain responsible for the activation of ...
... as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole ... While botulinum toxin is generally considered safe in a clinical setting, there can be serious side effects from its use. The ... Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically ... BotDB: extensive resources on BoNT structures, inhibitors, kinetics, and literature. *A consumer sociological investigation of ...
Another is ATF-2 which contains a transcriptional activation (ACT) domain and a basic zipper DNA-binding (bZip) domain with a ... Many cell generations later, in the absence of the inhibitor, the increased gene expression was still expressed, showing ... sets the local chromatin structure. In this way, acetylation patterns are transmitted and interconnected with protein binding ... HDAC10 has two catalytic domains as well. One active domain is located in the N-terminus and a putative catalytic domain is ...
Kehry M, Hodgkin P (1994). "B-cell activation by helper T-cell membranes". Crit Rev Immunol. 14 (3-4): 221-38. PMID 7538767.. ... "Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus" (PDF). Biochem Soc Trans. 31 (Pt 3): 716-8. PMID ... "Presence of secretory leukocyte protease inhibitor in human endometrium and first trimester decidua suggests an antibacterial ... sebagai set pelatihan.[139] ... cell antigen receptor signaling and activation of human T cells ...
... site-directed mutagenesis of the CX myosin-binding domain of MyBP-C". Journal of Muscle Research and Cell Motility. 20 (7): 703 ... Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718.. ... ACE-inhibitors or angiotensin II receptor blockers may be effective in reducing proteinuria when given at the early stage of ... three paralogs appear to bind the same or very similar light chains and share basic properties as to structure and activation, ...
Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a ... "Cell. 166 (4): 907-19. doi:10.1016/j.cell.2016.07.004. PMC 5418658. PMID 27499021.. ... The side perspective is a view from above and to the side of the GPCR as it is set in the plasma membrane (the membrane lipids ... guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these ...
Liu WM, Chu WM, Choudary PV, Schmid CW (May 1995). "Cell stress and translational inhibitors transiently increase the abundance ... June 2007). "Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs". Cell. 129 (7 ... The authors found that this activation involves a conformational alteration to the structure of HSR-1 in response to rising ... The GENCODE consortium has collated and analysed a comprehensive set of human lncRNA annotations and their genomic organisation ...
The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ... each with their own distinguishing set of cell surface markers (see below).[11] Subsequently, numerous new populations of ... "U.S. FDA Approved Immune-Checkpoint Inhibitors and Immunotherapies". Medical Writer Agency , 香港醫學作家 , MediPR , MediPaper Hong ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ...
In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring ... Organisms of the Archaea and Bacteria domain have no cell nucleus.[76]) It is hypothesized that the symbiosis originated when ... within the nucleus and degrade once there is a decrease in activity or if cells are treated with proteasome inhibitors.[29][51] ... "LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages". The ...
Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen ... National Center for Biotechnology Information, US National Library of Medicine, 2018 Set 8 7; CID 442195 (rev), pàgs: 24 [ ... Calmels C, Ventura M, Aknin C, Métifiot M, Andreola ML «De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain ... Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3» (en ...
... as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole ... While botulinum toxin is generally considered safe in a clinical setting, there can be serious side effects from its use. Most ... Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL (December 2010). "Small molecule inhibitors as countermeasures for ... Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically ...
Clone = a set of cells that all descend from a common ancestor cell. A clone is usually distinguished through inheritance of a ... 2006). "Glioma stem cells promote radioresistance by preferential activation of the DNA damage response". Nature. 444 (7120): ... which inihibit growth even in cell lines with mutations in EGFR), the combination of EGFR and MET kinase inhibitors, and Hsp90 ... "A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors". Cancer Res ...
... the host cell is destroyed by killer T cells and the virus-specific T-cells proliferate. Cells such as the macrophage are ... The complete set of viruses in an organism or habitat is called the virome; for example, all human viruses constitute the human ... Le Page C, Génin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Reviews in Immunogenetics. 2000;2(3):374- ... Magden J, Kääriäinen L, Ahola T. Inhibitors of virus replication: recent developments and prospects. Applied Microbiology and ...
DNA replication: Xenopus cell-free extracts also support the synchronous assembly and the activation of origins of DNA ... This approach was used to identify novel inhibitors of proteasome-mediated protein degradation and DNA repair enzymes.[74] ... The genus is also known for its polyploidy, with some species having up to 12 sets of chromosomes. ... "A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium ...
V-set Domain-containing T-cell Activation Inhibitor 1. A B7 antigen subtype that inhibits the costimulation of T-cell ... the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to ... cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling ... Summary of "The Role of PAR2 in TGF-β1-Induced ERK Activation and Cell Motility.". Recently, the expression of proteinase- ...
V-set domain containing T-cell activation inhibitor 1. Protein classi. Protein class the gene product belongs to according to ... V-set domain containing T-cell activation inhibitor 1 (HGNC Symbol). Entrez gene summary. This gene encodes a protein belonging ... Cell cycle intensity correlation. Cell cycle spatial correlation. Cell cycle biologically. Custom data cell cycle dependant. - ... GO:0042102 [positive regulation of T cell proliferation]. GO:0050868 [negative regulation of T cell activation]. GO:0072602 [ ...
Rabbit Polyclonal Anti-VTCN1 Antibody against Human V-set domain containing T cell activation inhibitor 1. Validated for IHC. ... T-cell costimulatory molecule B7x; VCTN1; V-set domain-containing T-cell activation inhibitor 1 ... Immunofluorescent staining of human cell line MCF7 shows localization to plasma membrane & cell junctions. ... Immunohistochemical staining of human breast shows moderate membranous positivity in glandular cells. ...
Protein Name:V-set domain-containing T-cell activation inhibitor 1 Catalog #:OASA00963 ... Phone: 1-858-552-6979 , Fax: 1-858-552-6975. Email: [email protected] , Technical support: [email protected] ...
V-Set Domain-Containing T-Cell Activation Inhibitor 1 - metabolism ...
VTCN1 (V-set domain containing T cell activation inhibitor 1)  Samarawardana, P; Shroyer, KR (Jean-Loup Huret (Editor-in-Chief ... COL16A1 (collagen, type XVI, alpha 1)  Grässel, S; Ratzinger, S (Jean-Loup Huret (Editor-in-Chief) ; INIST-CNRS (Publisher), ... IL22RA1 (interleukin 22 receptor, alpha 1)  Gelebart, P; Lai, R (Jean-Loup Huret (Editor-in-Chief) ; INIST-CNRS (Publisher), ...
V-set domain-containing T-cell activation inhibitor 1 is a protein that in humans is encoded by the VTCN1 gene. B7H4 belongs to ... "Entrez Gene: VTCN1 V-set domain containing T cell activation inhibitor 1". Maruyama K, Sugano S (January 1994). "Oligo-capping ... Prasad DV, Richards S, Mai XM, Dong C (June 2003). "B7S1, a novel B7 family member that negatively regulates T cell activation ... a widely expressed B7 family member that inhibits T cell activation". Proceedings of the National Academy of Sciences of the ...
VTCN1; V-set domain containing T-cell activation inhibitor 1 [KO:K06747] ... Cell-cell adhesions also underpin axon-axon contacts and link neurons with supporting schwann cells and oligodendrocytes.. ... Cell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic ... Furthermore cell-cell adhesions are important for brain morphology and highly coordinated brain functions such as memory and ...
V-set domain-containing T-cell activation inhibitor 1. Synonyms [1]. PRO1291, B7-H4, B7X, VCTN1, B7h.5, B7S1, B7H4 ... VTCN1 is an inclusion criterion in 1 clinical trial for breast carcinoma, of which 1 is open and 0 are closed. Of the trial ... VTCN1 is an inclusion criterion in 1 clinical trial for malignant solid tumor, of which 1 is open and 0 are closed. Of the ... VTCN1 is an inclusion criterion in 1 clinical trial for fallopian tube carcinoma, of which 1 is open and 0 are closed. Of the ...
T cell costimulatory molecule B7x; T-cell costimulatory molecule B7x; V-set domain-containing T-cell activation inhibitor 1; ... It is speculated that the costimulatory regulation of T cells by B7S1 is influenced by the activation status of B cells. While ... B7-H4 is expressed on activated T-cells, B-cells, monocytes and dendritic cells. Aberrant expression has been associated with ... Cell number should be determined empirically but can range from 10^5 to 10^8 cells/test. It is recommended that the antibody be ...
Human V-set domain containing T cell activation inhibitor 1 (B7-H4) ELISA Kit. 48T. 513.60 €. -. abelisa. ... Rabbit Metalloproteinase inhibitor 4 (TIMP4) ELISA Kit. 48T. 535.00 €. -. abelisa. AE14942HU. Human Tissue inhibitors of ... Horse Metalloproteinase inhibitor 2 (TIMP2) ELISA Kit. 48T. 535.00 €. -. abelisa. AE14958SH. Sheep Tissue inhibitors of ... Human Trypsinogen activation peptide (TAP) ELISA Kit. 48T. 535.00 €. -. abelisa. AE12056RA. Rat Usher syndrome type-1C protein- ...
It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system. ... stable cell line is clonally-derived from a CHO cell line, which has been transfected with an Anti-human VTCN1 F(ab) gene to ... VTCN1; V-set domain containing T cell activation inhibitor 1; V-set domain-containing T-cell activation inhibitor 1; B7 family ... VTCN1 V-set domain containing T cell activation inhibitor 1 [ Homo sapiens ]. ...
V-set domain containing T cell activation inhibitor 1. *Gene ID. *79679 ... It transmits an activation signal to the T cell after antigen is bound. CD3-zeta may not provide a fully competent activation ... CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ , ε chain, forms the TCR-CD3 complex ... TRAC-CAR-T Cell Development with CRISPR/Cas9 Technology: A novel technology to build more powerful CAR-T cells. ...
Chemical-registry-number] 0 / Antigens, CD80; 0 / Biomarkers, Tumor; 0 / V-Set Domain-Containing T-Cell Activation Inhibitor 1 ... Carcinoma, Small Cell / chemistry. Carcinoma, Small Cell / diagnosis. Carcinoma, Small Cell / genetics. Cystadenocarcinoma, ... MeSH-minor] Adenocarcinoma, Clear Cell / diagnosis. Adenocarcinoma, Clear Cell / immunology. Adenocarcinoma, Clear Cell / ... MeSH-minor] Adenocarcinoma, Clear Cell / immunology. Adenocarcinoma, Clear Cell / metabolism. Adenocarcinoma, Clear Cell / ...
T cell costimulatory molecule B7x. *V-set domain containing T cell activation inhibitor 1 ... extracellular domain (ECD) with one Ig-like V-set domain and one Ig-like C2-set domain, a 21 aa transmembrane segment, and a 2 ... 4-8). Following binding to activated T cells, B7-H4 serves as a co‑inhibitor of the T cell response. This is accomplished by ... B7-H4 is expressed on the surface of activated lymphocytes, macrophages, monocytes, dendritic cells, epithelial cells, and bone ...
Ab191634 is an active protein fragment produced in HEK 293 cells and has been validated in FuncS, SDS-PAGE. Abcam… ... T-cell costimulatory molecule B7x. *V set domain-containing T cell activation inhibitor 1 ... Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and ... and non-small-cell lung cancers (NSCLC). Expressed on activated T- and B-cells, monocytes and dendritic cells, but not ...
VTCN1 (V-set domain containing T cell activation inhibitor 1). Samarawardana P, Shroyer KR. http://atlasgeneticsoncology.org/ ... SEMA4D (sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D). ... SEMA3F (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F). Potiron VA, Drabkin HA, Roche ... NSD2 (nuclear receptor binding SET domain protein 2 ). Martinez-Garcia E, Licht JD. http://atlasgeneticsoncology.org/Genes/ ...
In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of ... MEK cells (Null), Pkd1. -heterozygous PH2 cells, and Pkd1. -homozygous PN24 cells (top panel). Relative SMYD2 expression was ... SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased ... Targeting SMYD2 with its specific inhibitor, AZ505, delayed cyst growth in both early- and later-stage Pkd1 conditional ...
V-set domain containing T cell activation inhibitor 1. Aliases:. B7-H4, B7H4, B7S1, B7X, B7h.5, FLJ22418, PRO1291, VCTN1. ... Proteins in this family are present on the surface of antigen-presenting cells and interact with ligand bound to receptors on ... the surface of T cells. Studies have shown that high levels of the encoded protein has been correlated with tumor progression. ...
... or deletion of the enzymatic SET domain, destabilizes MLL3/4 proteins and prevents enhancer activation in cell differentiation ... an inhibitor of H3K4 methylation, ... cell-type-specific gene expression, and cell differentiation ( ... Enhancers control cell-type-specific gene expression and are critical for cell differentiation and tissue development. Primed ... We also use adipogenesis and mouse embryonic stem (ES) cells as model systems to understand epigenomic regulation of cell fate ...
V-Set Domain-Containing T-Cell Activation Inhibitor 1 v-sis Genes use Genes, sis ... Vesicular Glutamate Transporter 1 use Vesicular Glutamate Transport Protein 1 Vesicular Glutamate Transporter 2 use Vesicular ... Voltage-Gated Sodium Channel Type 1 Subunit alpha use NAV1.1 Voltage-Gated Sodium Channel ...
V-Set Domain-Containing T-Cell Activation Inhibitor 1 v-sis Genes use Genes, sis ... Vesicular Glutamate Transporter 1 use Vesicular Glutamate Transport Protein 1 Vesicular Glutamate Transporter 2 use Vesicular ...
V-set domain containing T cell activation inhibitor 1. 0.016. Cxcl13. chemokine (C-X-C motif) ligand 13. 0.016. ... inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon. 0.073. ... membrane-spanning 4-domains, subfamily A, member 3 (hematopoietic cell-specific). 0.032. ... nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon. 0.203. ...
V-set domain containing T cell activation inhibitor 1. Mentions: We parsed the differentially expressed genes into pathways, ... V-set domain containing T cell activation inhibitor 1. ... CDC20 cell division cycle homolog 20; CXCL14, chemokine (c-x-c ... Apyrase, ATP diphosphohydorlase; ANAPC2, anaphase promoting complex subunit 2; CDC20 cell division cycle homolog 20; CXCL14, ... SH2 domain containing 3C; SLC6A6, solute carrier family 6; TP53 tumor protein p53; TP53RK, TP53 regulating kinase; VTCN1, ...
V-Set Domain-Containing T-Cell Activation Inhibitor 1. Substances. *Antigens, CD ... T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or ... Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell ... the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory ...
... which effectively reorganizes the actin cytoskeleton of the cell. In the case of neurons, activation of this pathway results in ... domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. As a transmembrane protein, it can mostly be found ... To be able to understand how these components regulate signalling processes an experiment has been set up "model of serum ... Known interactions are with proteins such as Oligodendrocyte-myelinn glycoprotein, Nogo-A (neurotic outgrowth inhibitor), and ...
  • RAS -RAF-MEK-extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. (bioportfolio.com)
  • BRAF V600E inhibition stimulates AMP-activated protein kinase (show PRKAA2 ELISA Kits )-mediated autophagy in colorectal cancer cells. (antibodies-online.com)
  • The JAKs are structurally unique in having a C-terminal kinase domain (JH1) preceded by a pseudokinase domain (JH2), which lacks catalytic activity but has a critical regulatory function. (thermofisher.com)
  • The V617F mutation in the JH2 pseudo-kinase domain of JAK2 was found in a high percentage of patients with myeloproliferative disorders, including polycythaemia vera [10] . (thermofisher.com)
  • LINGO-1 is involved in the regulation of neural apoptosis by inhibiting WNK3 kinase activity. (wikipedia.org)
  • This approach has led to the discovery of novel inhibitors of the inflammatory disease kinase, RIPK2, and more recently to novel mechanisms to inhibit the pyroptotic pore protein, Gasdermin D. Both of these pharmaceutical intervention show efficacy in inflammatory diseases as diverse as Inflammatory Bowel Disease, Psoriasis, Sarcoidosis and Sepsis. (case.edu)
  • Significant effort has focused on the development of kinase inhibitors directed against several proteins downstream of KRAS, including the RAF-MAPK and PI3K-AKT signaling cascades ( 3 ). (aacrjournals.org)
  • The present invention relates to an isolated nucleic acid molecule (polynucleotide) which encodes a human receptor tyrosine kinase, KDR, which is expressed on human endothelial cells. (google.es)
  • The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. (sciencemag.org)
  • Here, we examine the protein-protein interactions required for regulation of an Aplysia bag cell neuron cation channel by a closely associated protein kinase C (PKC). (jneurosci.org)
  • In inside-out patches, the PKC-dependent enhancement of cation channel open probability could be prevented by the src homology 3 (SH3) domain, presumably by disrupting a link between the channel and the kinase. (jneurosci.org)
  • In the present work, we investigate the interactions between a cation channel, which is responsible for prolonged changes in Aplysia bag cell neuron excitability, and a closely associated kinase. (jneurosci.org)
  • To determine whether the association between the kinase and the cation channel involves specific forms of protein-protein interactions, we have tested the ability of different interaction domains and motifs to interfere with the functional link between channel and kinase in excised, inside-out patches. (jneurosci.org)
  • Our data indicate that the cation channel-kinase "association" requires src homology 3 (SH3) domain protein-protein interactions, and that disruption of this interaction prevents channel modulation and attenuates the long-lasting depolarization produced by cation channel activation. (jneurosci.org)
  • Many different signaling molecules can induce cell migration by activating the small GTPase Ras, which in turn activates both phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways. (rupress.org)
  • discovered that a downstream component of the ERK pathway, p90 ribosomal S6 kinase (RSK) phosphorylates and inactivates an inhibitor of cell migration called SH3P2 ( 3 ). (rupress.org)
  • The immediate‐early (IE) genes c‐ fos and c ‐jun are rapidly induced in mammalian cells via ERK or p38 MAP kinase cascades. (embopress.org)
  • The phosphatidylinositol 3-kinase (PI3K) pathway plays a pivotal role in the maintenance of processes such as cell growth, proliferation, survival, and metabolism in all cells and tissues. (hindawi.com)
  • The phosphatidylinositol (PI) 3-kinase (PI3K) signaling pathway is a normal signal transduction cascade that exists in all types of cells and is physiologically involved in cell proliferation, survival, protein synthesis, metabolism, differentiation, and motility. (hindawi.com)
  • Pleckstrin homology domain leucine-rich repeat protein phosphatase functions as a "brake" for Akt and protein kinase C signaling, which has been extensively reviewed [ 16 ]. (hindawi.com)
  • Studies have demonstrated that Wnt/β-catenin is able to regulate a number of downstream targets including cyclin D1, Myc proto-oncogene protein and mitogen-activated protein kinase 8, which regulates cell proliferation, migration and stemness ( 16 - 18 ). (spandidos-publications.com)
  • In contact with the TCR/CD3 signaling machinery, CD5 and CD6 are very rapidly phosphorylated on tyrosine residues (19, 24), presumably from the SRC-family kinase LCK, with the concomitant docking of intracellular mediators that contain SH2 domains, semi-autonomous conserved structural domains that bind to phosphorylated tyrosine residues. (cura-cancer.com)
  • NF-kappa-B essential modulator ( NEMO ) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene . (wikidoc.org)
  • NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. (wikidoc.org)
  • Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). (cellsignal.com)
  • Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7). (cellsignal.com)
  • 1-4 Its biological effects are mediated by a set of tyrosine kinase receptors (ErbB2, ErbB3, and ErbB4) that dimerize on ligand binding, leading to phosphorylation and downstream signaling. (ahajournals.org)
  • On dimerization, the intrinsic kinase domain is activated, resulting in phosphorylation of specific tyrosine residues within the cytoplasmic tail of the receptor and subsequent downstream signaling. (ahajournals.org)
  • In mammalian cells, the UPR is divided into 3 primary signaling branches: (i) inositol requiring kinase 1 alpha (IRE1a) that activates XBP1, (ii) eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) that activates activating transcription factor 4 (ATF4), and (iii) activating transcription factor 6 (ATF6) as both the sensor and the transcription factor. (mdanderson.org)
  • At the molecular level, the cytosolic domain of IRE1a has dual enzymatic activities, consisting of a serine/threonine kinase domain and a C-terminal ribonuclease (RNase) domain. (mdanderson.org)
  • Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3′ kinase, and phospholipase C-γ1. (rupress.org)
  • A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. (bioportfolio.com)
  • A large superfamily of cell surface membrane proteins characterized by their four transmembrane domains. (bioportfolio.com)
  • These proteins are expressed on the surface of antigen-presenting cells and interact with ligands (e.g. (wikipedia.org)
  • Cell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, embryogenesis, and development of neuronal tissue. (genome.jp)
  • Membrane proteins that mediate immune cell-cell interactions fall into different categories, namely those involved in antigen recognition, costimulation and cellular adhesion. (genome.jp)
  • Proteins in this family are present on the surface of antigen-presenting cells and interact with ligand bound to receptors on the surface of T cells. (bio-rad.com)
  • Ectopic expression of H3.3K4M, an inhibitor of H3K4 methylation, or deletion of the enzymatic SET domain, destabilizes MLL3/4 proteins and prevents enhancer activation in cell differentiation ( NAR 2019 ). (nih.gov)
  • The state whereby activator BH3 proteins are sequestered by antiapoptotic Bcl-2 proteins has been termed "primed for death" because such cells are paradoxically sensitized to select BH3 proteins ( 10 ). (aacrjournals.org)
  • Of note, most nontransformed cells lack BH3 priming, providing a conceptual therapeutic index for agents that antagonize the antiapoptotic Bcl-2 proteins ( 11 ). (aacrjournals.org)
  • STAT proteins contain a SH2 domain for dimerization and a DNA-binding domain. (thermofisher.com)
  • One mechanism for negative regulation of JAK-STAT pathways is through suppresser of cytokine signaling (SOCS) proteins, which directly bind to and inactivate JAKs [5] , and protein inhibitors of activated STATs (PIAS) that bind to phosphorylated STAT dimers, preventing DNA binding [6] . (thermofisher.com)
  • This tyrosine phosphorylation promotes STAT homo and heterodimerization mediated by reciprocal phosphotyrosine SH2 domain interaction and the dissociation of the dimers from the receptor complex (D). The STAT dimer is then translocated to the cell nucleus, where they complex with other nuclear proteins and regulate gene expression by binding to promoters or other response elements on DNA. (thermofisher.com)
  • Proteins derived from ORFs 1 to 4 showed no difference in Gα q inhibitory potential or recruitment from the nucleus in response to Gα q signaling. (aspetjournals.org)
  • By comparison, simply constructed RGS proteins in the RGSZ-like and RGS4-like (R4/B) subfamilies consist of little more than an RGS domain flanked by short (typically 10-70 residues) amino- and carboxyl-terminal extensions. (aspetjournals.org)
  • T cell activation and immune function are regulated by the innate immune system through positive and negative costimulatory proteins. (biomol.com)
  • The C-terminal LRR domain is essential for the protein's function with its screening for proteins that interact with this domain. (wikipedia.org)
  • The human TREM gene cluster is located on chromosome 6p21.1 and encodes for six different proteins, TREM 1-5 and TREM-like transcript-1 (TLT-1) ( 5 ). (jimmunol.org)
  • Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. (aacrjournals.org)
  • Unlike the majority of plant Myb-like proteins, these Myb proteins, NtmybA1, NtmybA2, and NtmybB, have three imperfect repeats in the DNA binding domain, as in animal c-Myb proteins. (plantcell.org)
  • Phase-specific transcription may contribute to an orderly progression through the cell cycle by ensuring that key proteins are produced in a strict temporal sequence. (plantcell.org)
  • however, their role in vivo in mammalian cells appears to involve deacetylation of other proteins or transcription factors, e.g. , p53, rather than histones ( 15 , 16 ). (aacrjournals.org)
  • All DVL proteins contain three conserved domains: DIX, PDZ, and DEP. (asm.org)
  • The smooth identification and low-cost production of highly specific agents that interfere with signaling cascades by targeting an active domain in surface receptors, cytoplasmic and nuclear effector proteins, remain important challenges in biomedical research. (mdpi.com)
  • SH3 and PDZ domains from other proteins were ineffective. (jneurosci.org)
  • In eukaryotic cells, the aggregation of the endoplasmic reticulum (ER)-mediated unfolded or misfolded proteins leads to disruption of the ER homeostasis, which can trigger ER stress. (intechopen.com)
  • Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high precision spatiotemporal control of many cellular functions 1 - 11 . (pubmedcentralcanada.ca)
  • In principle, the genomic anchor may also be replaced with other DNA binding domains such as zinc finger proteins 16 or RNA-guided DNA binding domains based on nucleolytically inactive mutants of Cas9 ( Extended Data Fig. 1 ) 18 - 22 . (pubmedcentralcanada.ca)
  • They are studied by chromatin immunoprecipitation (ChIP) to define their location, by genetic and biochemical analyses to identify enzymes involved and by identification of binding proteins or domains to determine their molecular function. (embopress.org)
  • The SET domain is found in many proteins now demonstrated to mediate lysine-directed histone methylation. (sdbonline.org)
  • ALL-1 is present within a stable, very large multiprotein supercomplex composed of ~29 proteins. (sdbonline.org)
  • Strikingly, most ALL-1-associated proteins can be classified into well-known complexes involved in transcription. (sdbonline.org)
  • Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). (cellsignal.com)
  • Type I and II NRGs contain an immunoglobulin-like domain and are single-pass transmembrane proteins. (ahajournals.org)
  • Type III NRGs, containing a cysteine-rich domain, are 2-pass transmembrane proteins. (ahajournals.org)
  • When unfolded/misfolded proteins accumulate in the ER, IRE1a auto-phosphorylates and activates the RNase domain. (mdanderson.org)
  • These proteins differ from the classical cadherins in that they possess varying numbers of extracellular cadherin (EC) repeats and have divergent cytoplasmic domains. (jneurosci.org)
  • Polyclonal antibodies against TAF1 (Active Motif, Carlsbad, CA) or the cytoplasmic domain of NFPC, followed by incubation with a fluorescent secondary (goat anti-rabbit IgG AlexaFluor594, Invitrogen, Carlsbad, CA) were used to detect these proteins using standard protocols. (jneurosci.org)
  • Erythroid Krüppel-like factor (EKLF) is an erythroid cell-specific transcription factor that plays a critical role in β-globin gene activation via its interactions with CBP/p300 and SWI/SNF proteins. (asm.org)
  • Background: The Bcl-2 family consists of a number of evolutionarily conserved proteins containing Bcl-2 homology domains (BH) that regulate apoptosis through control of mitochondrial membrane permeability and release of cytochrome c (1-3). (cellsignal.com)
  • Interactions between death-promoting and death-suppressing Bcl-2 family members has led to a rheostat model in which the ratio of pro-apoptotic and anti-apoptotic proteins controls cell fate (4). (cellsignal.com)
  • Although B7-H4 binds an unknown receptor, it is thought to deliver an inhibitory signal to T-cells preventing their proliferation, cell cycle progression and interleukin-2 production. (thermofisher.com)
  • Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. (creativebiomart.net)
  • SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased cystic renal epithelial cell proliferation and survival. (jci.org)
  • STAT3 modulates the transcription of a wide variety of regulatory genes involved in cell proliferation, differentiation, migration, apoptosis, and other critical cellular functions. (ntu.edu.sg)
  • Accordingly, matrix-surface-bound VTCN1-Ig fusion protein suppressed the proliferation of islet-specific T cell clones derived from T1D patients. (beloranib.net)
  • Specifically, a gradual loss of membrane-tethered VTCN1 due to a proteolytic cleavage mediated by metalloproteinase nardilysin (NRD1), progressed alongside natural T1D development, and triggered hyper-proliferation of diabetogenic T cells (22). (beloranib.net)
  • These cytokines and growth factors are responsible for various cellular functions, including proliferation, growth, hematopoiesis, and immune response [1-4] . (thermofisher.com)
  • Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells in the bone marrow ( Figure 1 ) and, usually, the presence of a monoclonal Ig in the blood and/or urine. (asnjournals.org)
  • Additional name(s) for this target protein: V-set domain containing T cell activation inhibitor 1 Protein function: Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production. (biomol.com)
  • Our research program focuses on the mechanisms that control the proliferation of mammalian cells under normal and pathological conditions (regeneration, cancer), with a particular emphasis on stem cells and gene regulatory networks. (stanford.edu)
  • Functionally, over-expression of SETDB1 significantly promoted the proliferation and migration of CRC cells in vitro and in vivo , while knocking down SETDB1 suppressed their growth. (jcancer.org)
  • Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that function as transcription factors regulating the expression of genes involved in lipid biosynthesis, glucose metabolism, as well as cell proliferation, differentiation, and survival [ 1 - 4 ]. (hindawi.com)
  • Overexpression of TRIM37 induced cell proliferation and drug resistance ability of OS cells, whilst TRIM37 knockdown suppressed cell growth rate and restored chemosensitivity. (spandidos-publications.com)
  • CREPT overexpression is associated with proliferation behaviors and poor prognosis in non-small cell lung cancer. (amedeo.com)
  • Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma. (amedeo.com)
  • The miR-203 inhibits cell proliferation, invasion, and migration of non-small cell lung cancer by downregulating RGS17. (amedeo.com)
  • Neuregulin-1 (NRG-1) is a member of the epidermal growth factor (EGF) family known to activate proliferation, differentiation, and survival of many tissue types, including breast epithelial cells, glial cells, neurons, and myocytes. (ahajournals.org)
  • Finally, inducible expression of EKLF yields cells with a decreased proliferation rate ( 14 ). (asm.org)
  • Functional network of genes modulating GAS QTL.Graphical representation of the molecular relationships between differentially expressed genes, showing the central role of IL-1, IL-1rn, PTGES, and PTGES2 in modulating response to GAS sepsis and their indirect interactions with IFN-γ and IL-2 networks in modulating bacterial sepsis. (nih.gov)
  • a critical threshold for inhibition of MAPK (show MAPK1 ELISA Kits ) signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. (antibodies-online.com)
  • STATs then dimerize, translocate to the nucleus, bind to the consensus DNA sequence of 5'-TT(N4-6)AA-3' and initiate the transcription of target genes [1-4] . (thermofisher.com)
  • However, activation of one of the three cyclin D genes has been shown to be present in nearly all myeloma cases. (asnjournals.org)
  • Prompted by significant changes in the expression of genes involved in Ca 2+ and cyclic AMP (cAMP) signaling pathways in CAD-resistant MCF7 breast cancer cells, we identified here an early lysosomal Ca 2+ release through P2X purinergic receptor 4 (P2RX4) and subsequent Ca 2+ - and adenylyl cyclase 1 (ADCY1)-dependent synthesis of cAMP as a signaling route mediating CAD-induced lysosomal membrane permeabilization and cell death. (aacrjournals.org)
  • Some of these studies will include an evaluation of how cells control the way that genes are expressed, how cells 'know' to become retinal cells, how cells remain retinal cells, how cells lose their identity as retinal cells, what changes make retinoblastoma cells different from normal retinal cells, and what changes make some retinoblastomas worse than others. (stanford.edu)
  • While a graduate student, he studied the breast cancer genes BRCA1 and BRCA2, ultimately attaining a Ph.D. in Cell Biology. (case.edu)
  • Plant B-type cyclin genes are expressed specifically in late G2- and M-phases during the cell cycle. (plantcell.org)
  • In this study, we show that G2/M-phase-specific activation of the NACK1 promoter also is regulated by the MSA element, suggesting that a defined set of G2/M-phase-specific genes are coregulated by an MSA-mediated mechanism. (plantcell.org)
  • During the cell cycle, the level of NtmybB mRNA did not change significantly, whereas the levels of NtmybA1 and A2 mRNAs fluctuated and peaked at M-phase, when B-type cyclin genes were maximally induced. (plantcell.org)
  • From yeast to humans, progression through the cell cycle is associated with the phase-specific transcription of defined sets of genes ( McKinney and Heintz, 1991 ). (plantcell.org)
  • During the G1-to-S transition, a set of specific genes are induced, including G1 cyclin genes and several genes involved in DNA synthesis in yeast ( Koch and Nasmyth, 1994 ), animal ( Müller, 1995 ), and plant cells ( Ito, 1998 ). (plantcell.org)
  • Ramirez-Parra and Gutierrez, 2000 ) supports the idea that plants have evolved a mechanism for G1/S-phase-specific transcription that relies on genes analogous to those acting in animal cells. (plantcell.org)
  • Later in the cell cycle, during G2- and M-phases, another set of genes is expressed, among which B-type cyclin genes are the best characterized. (plantcell.org)
  • As many genes were down-regulated as up-regulated by HDAC inhibitor treatment. (aacrjournals.org)
  • Comparison of the data sets defined a common ("core") set of 13 genes regulated by all of the HDAC inhibitors in three cell lines, 8 up-regulated and 5 down-regulated. (aacrjournals.org)
  • Ten of 13 genes were confirmed in dose response studies in T24 cells by quantitative-PCR. (aacrjournals.org)
  • The core regulated genes are involved predominantly in cell cycle/apoptosis and DNA synthesis in response to HDAC inhibitors. (aacrjournals.org)
  • Inhibitors of the HDACs are able to de-repress these genes resulting in antiproliferative effects in vitro and antitumor effects in vivo ( 3 - 6 ). (aacrjournals.org)
  • HDAC inhibitors induce the hyperacetylation of nucleosomal histones in cells resulting in the expression of repressed genes that produce growth arrest, terminal differentiation, and/or apoptosis in carcinoma cells ( 2 , 3 , 17 ). (aacrjournals.org)
  • It is generally believed that colorectal carcinogenesis is a multiple-step process and caused by activation of oncogenes and silencing of tumor suppressor genes due to accumulation of various genetic mutations and epigenetic alterations [ 7 , 8 ]. (jcancer.org)
  • In this study, we conducted expression profiling of immunotherapy-related genes, including those in Th1/2 helper T and regulatory T cells, and stimulatory and inhibitory checkpoint molecules associated with survival prediction in 571 patients with malignant and aggressive form of gliomas, glioblastoma multiforme (GBM). (cdc.gov)
  • Expression profiling and Random forests analysis of 21 immunosuppressive genes and Kaplan-Meier analysis in 158 patients in the training data set suggested that CD276, also known as B7-H3, could be a single gene marker candidate. (cdc.gov)
  • Furthermore, prognosis prediction formulas, composed of Th2 cell-related GATA transcription factor 3 (GATA3) and immunosuppressive galactose-specific lectin 3 (LGALS3), based on 67 immunotherapy-related genes showed poor survival with high scores in training data set, which was also validated in another 413 patients in the test data set. (cdc.gov)
  • In addition, inhibitory checkpoint genes, including T cell immunoreceptor with Ig and ITIM domains, V-set domain containing T cell activation inhibitor 1, T-cell immunoglobulin and mucin-domain containing 3, and tumor necrosis factor receptor superfamily 14, showed potential as secondary marker candidates. (cdc.gov)
  • Plays a central role in the transcriptional activation of genes such as collagenase or insulin. (string-db.org)
  • Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. (string-db.org)
  • One of the activated genes is an inhibitor of cyclin-dependent kinases. (string-db.org)
  • Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. (embopress.org)
  • TRIM37‑regulated genes were subsequently analyzed by expression microarray and gene set enrichment analysis. (spandidos-publications.com)
  • Among the genes identified, SFRP1 was specifically indicated to target β-catenin, and thus might be targeted by epigenetic therapy in NSCLC cell lines. (biomedcentral.com)
  • This study performed a meta-analysis of reprogrammed NSCLC cell lines to identify genes associated with epigenetic alterations and expression changes during reprogramming and to identify promising candidate genes for targets of epigenetic therapy. (biomedcentral.com)
  • The activated RNase domain excises a 26-bp intron from the XBP1 mRNA in metazoans and causes a translational frame-shift that results in the production of the spliced/activated form of XBP1 protein (XBP1s), an active transcription factor responsible for the induction of a specific set of target genes. (mdanderson.org)
  • Histone acetylation correlates with gene activation while methylation correlates with either activation or repression, depending on the specific lysine (K) residue that gets methylated. (nih.gov)
  • Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1. (frontiersin.org)
  • Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens, such as those on microbial pathogens, and generation of pathogenic autoantibodies, IgE in allergic reactions, as well as B cell neoplasia. (frontiersin.org)
  • Histone modification is a common epigenetic event in mammalian cells [ 12 ], including acetylation and deacetylation, methylation and demethylation, phosphorylation, ubiquitination and so on, which play an important role in maintaining genomic stability [ 13 , 14 ]. (jcancer.org)
  • Generally, methylation of H3K4, H3K36 and H3K79 is associated with gene activation, whereas methylation of H3K9, H3K27 and H4K20 usually leads to gene inactivation [ 16 ]. (jcancer.org)
  • SETDB1 protein belong to the SET-domain ( S u(var)3-9, E (z), T hrithorax) protein methyltransferase family [ 17 ], which is mainly involved in tri-methylation of H3K9 and usually cause gene silencing or transcription inhibition. (jcancer.org)
  • H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. (string-db.org)
  • therefore, as promoter methylation often reflects the effect of histone modification [ 9 ], a data set containing gene expression and promoter methylation information was analysed. (biomedcentral.com)
  • This methylase activity is associated with Hox gene activation and H3 (Lys4) methylation at cis-regulatory sequences in vivo. (sdbonline.org)
  • The Hox c8 promoter is necessary and sufficient for MLL responsiveness and, along with the 5' enhancer, exhibits differential histone acetylation and H3 (Lys4) methylation in Mll +/+ as compared to Mll -/- cells. (sdbonline.org)
  • Reexpression of MLL in null cells results in methylation of H3 (Lys4) at the Hox c8 5' enhancer and promoter as well as at other Hox gene promoters. (sdbonline.org)
  • H3 (Lys4) methylation is dependent on an intact MLL SET domain and this methyltransferase activity is stimulated by H3 peptides that are acetylated at Lys9 or Lys14. (sdbonline.org)
  • The complex's H3-K4 methylation activity is conferred by the ALL-1 SET domain. (sdbonline.org)
  • Arginine methylation of histones H3 (Arg2, 17, 26) and H4 (Arg3) promotes transcriptional activation and is mediated by a family of protein arginine methyltransferases (PRMTs), including the co-activators PRMT1 and CARM1 (PRMT4) (4). (cellsignal.com)
  • Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. (nature.com)
  • Mono-, di-, or tri-methylation of lysine side chains in histones can be associated with either transcriptional activation or repression depending on the specific lysine residue modified and the degree of methylation. (nature.com)
  • Protease-activated receptor 2 (PAR2) is expressed by different cell types in the lungs and can mediate i. (bioportfolio.com)
  • Cigarette smoke extract enhances neutrophil elastase-induced IL-8 production via proteinase-activated receptor-2 upregulation in human bronchial epithelial cells. (bioportfolio.com)
  • Prostanoid-dependent bladder pain caused by proteinase-activated receptor-2 activation in mice: Involvement of TRPV1 and T-type Ca2+ channels. (bioportfolio.com)
  • The vector of anti-VTCN1 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human VTCN1. (creative-biolabs.com)
  • On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigen-nonspecific chimeric antigen receptor T-cells to significantly increases antitumor activity. (creative-biolabs.com)
  • CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ , ε chain, forms the TCR-CD3 complex. (creative-biolabs.com)
  • Angiotensin-converting Enzyme 2 (ACE2)-CHO Cell Line Model for COVID-19: Helps researchers to further study the interaction between the receptor ACE2 and the COVID-19 virus. (creative-biolabs.com)
  • These phosphorylated tyrosine residues provide paired docking sites for STAT via its SH2 domain (C). STAT, recruited to the receptor complex, is then phosphorylated at a tyrosine residue by the JAKs. (thermofisher.com)
  • Importantly, pharmacologic and genetic means to increase cellular cAMP levels either by activating cAMP-inducing G-protein-coupled receptors (GPR3 or β 2 adrenergic receptor) or ADCY1, or by inhibiting cAMP-reducing guanine nucleotide-binding protein G(i) subunit α2, C-X-C motif chemokine receptor type 4, or cAMP phosphodiesterases, sensitized cancer cells to CADs. (aacrjournals.org)
  • LINGO-1 is a functional component of the Nogo (neurite outgrowth inhibitor) receptor also known as the reticulon 4 receptor. (wikipedia.org)
  • LINGO-1 is a co-receptor that interacts with the ligand-binding Nogo-66 receptor (NogoR) in the Nogo receptor signaling complex. (wikipedia.org)
  • It has been shown that blocking the extracellular domain of LINGO-1 disrupts the interaction between receptor kinases and LINGO-1 which directly attenuates inhibition of neuronal survival. (wikipedia.org)
  • The triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role during the onset of sepsis by amplifying the host immune response. (jimmunol.org)
  • Some of the potential candidates acting as amplifiers of the innate immune response belong to the triggering receptor expressed on myeloid cells (TREM) family ( 1 - 4 ). (jimmunol.org)
  • We hypothesized that immune cell activation is specifically suppressed in the postischemic kidney, for example, by single Ig IL-1-related receptor (SIGIRR). (jimmunol.org)
  • TLR signaling involves either of the two cytoplasmic adaptor molecules MyD88 or Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) that facilitate the activation of MAPK, NF-κB, or IFN-related factors ( 3 ). (jimmunol.org)
  • Single Ig IL-1-related Receptor (SIGIRR), also known as Toll-IL-1 receptor 8 (TIR8), is a member and inhibitor of the TLR/IL-R family that is highly expressed in the kidney ( 15 , 16 , 17 ). (jimmunol.org)
  • Furthermore, berberine also suppressed the toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (Myd88)/nuclear factor (NF)-κB signaling pathway which was activated during the conversion of THP-1 cells to macrophages by PMA. (spandidos-publications.com)
  • Toll-like receptor 4 (TLR4), an intensively investigated member of the TLR family, serves a critical role in initiating inflammation ( 9 ) and participates in mediating inflammatory cell formation ( 10 ). (spandidos-publications.com)
  • Pursuing T cell receptor triggering, T cell activation is set up and amplified with the assembly on the TCR/CD3 macrocomplex of a variety of stimulatory enzymes that switch on many signaling cascades. (cura-cancer.com)
  • Maybe this aggregation of kinases in the cytoplasmic tail of CD5 and CD6 clarifies the behavior CPI-613 enzyme inhibitor observed in their initial characterization when either receptor, when induced together with the TCR/CD3 complex with monoclonal antibodies, amplified the activation signals originated in the TCR complex. (cura-cancer.com)
  • 9 A common motif to all NRG isoforms is the EGF-like receptor binding domain. (ahajournals.org)
  • Proteolytic cleavage by a member of the ADAM family results in the release of a bioactive fragment containing the EGF-like receptor binding domain. (ahajournals.org)
  • Cleavage of type III isoforms generates a transmembrane N-terminal fragment that includes the EGF-like receptor binding domain (symbolized as white fragments in the black NRG-1 bars). (ahajournals.org)
  • Synaptic transmission is dynamically modulated by neuropeptides, which often act on receptors that belong to the G protein-coupled receptor (GPCR) family ( 1 ). (pnas.org)
  • Another member of the membrane GC family, GC-A (also named NPR-A), is the receptor for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), and its activation reduces blood pressure and volume in the cardiovascular system ( 7 ⇓ - 9 ). (pnas.org)
  • DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8 + T cells, and other immune cells. (rupress.org)
  • a nucleotide-binding domain and leucine-rich-repeat [NLR] or AIM2-like receptor [ALR] family member), an adaptor protein (ASC/TMS1), and pro-caspase-1. (cellsignal.com)
  • To understand the genomic effects of HDAC inhibition on gene transcription we studied the gene expression profiles of T24 bladder and MDA breast carcinoma cells treated with three HDAC inhibitors, suberoylanilide hydroxamic acid, trichostatin A, and MS-27-275. (aacrjournals.org)
  • These data will aide in understanding the complex set of events in cells in response to chromatin remodeling induced by HDAC inhibition, which may be responsible for antitumor effects. (aacrjournals.org)
  • This phenomenon is regulated tightly by the balance of histone acetyltransferase and HDAC 2 activities ( 1 , 2 ). (aacrjournals.org)
  • The role of chromatin remodeling in carcinogenesis is based primarily on experiments with HDAC inhibitors, e.g. , sodium butyrate and TSA. (aacrjournals.org)
  • Several HDAC inhibitors exhibit antitumor effects in preclinical animal models including methylnitrosourea-induced breast carcinogenesis ( 4 , 21 , 22 ). (aacrjournals.org)
  • A histone deacetylase inhibitor might reactivate SFRP1 based upon the re-analysis of a public domain data set. (biomedcentral.com)
  • Unexpectedly, it also interacts with Sin3A and histone deacetylase 1 (HDAC1) corepressors via its zinc finger domain. (asm.org)
  • Given the molecular and genetic evidence for EKLF activation, it was unexpected to find that EKLF can also interact with corepressors (Sin3A and histone deacetylase 1 [HDAC1]) and transcriptionally repress promoters in vivo ( 13 ). (asm.org)
  • Recently, we unveiled an endogenous pathway of functional VTCN1 inactivation in APCs (particularly in macrophages C Ms, and dendritic cells C DCs) of NOD mice and T1D patients. (beloranib.net)
  • CAD-induced inhibition of lysosomal acid sphingomyelinase is necessary, but not sufficient, for the subsequent lysosomal membrane permeabilization and cell death, while other pathways regulating this cell death pathway are largely unknown. (aacrjournals.org)
  • These data reveal a previously unrecognized lysosomal P2RX4- and ADCY1-dependent signaling cascade as a pathway essential for CAD-induced lysosome-dependent cell death and encourage further investigations to find the most potent combinations of CADs and cAMP-inducing drugs for cancer therapy. (aacrjournals.org)
  • Consistent with this model, activation of Gα s /ACV but not Gα q signaling increased the relative abundance of the full-length RGS2 protein, suggesting that alternative translation initiation of RGS2 is part of a novel negative feedback control pathway for adenylyl cyclase signaling. (aspetjournals.org)
  • In contrast, non‐canonical autophagy is a pathway through which LC 3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC 3‐associated phagocytosis. (embopress.org)
  • On the contrary, multiple DEP domain mutants deficient in the planar cell polarity (PCP) pathway could fully rescue the Wnt3a response. (asm.org)
  • In the Wnt/β-catenin pathway, DVL is essential for the phosphorylation of the intracellular domains of LRP5 and LRP6. (asm.org)
  • The PI3K pathway stimulates actin polymerization and the formation of a lamellipodial protrusion at the leading edge of the cell, but how ERK signaling promotes cell motility is less well understood. (rupress.org)
  • now reveal that one function of the ERK pathway is to inactivate a negative regulator of the myosin Myo1E, allowing the motor protein to move to the tips of lamellipodia where it can facilitate cell movement ( 1 ). (rupress.org)
  • Upon activation of the ERK pathway, RSK phosphorylates a serine residue near to this C-terminal acidic patch in SH3P2, potentially disrupting the interaction with Myo1E. (rupress.org)
  • Indeed, ERK activation reduced the association between SH3P2 and Myo1E, an effect that could be prevented by adding an inhibitor of the ERK signaling pathway or by expressing a nonphosphorylatable version of SH3P2. (rupress.org)
  • In conclusion, berberine reduced NLRP3 inflammasone expression by suppressing the activation of the TLR4/Myd88/NF-κB signaling pathway in PMA-induced macrophages. (spandidos-publications.com)
  • This aberrant activation of PI3K/Akt pathway is primarily caused by loss of function of all negative controllers known as inositol polyphosphate phosphatases and phosphoprotein phosphatases. (hindawi.com)
  • Using the Wnt/β‑catenin inhibitor XAV‑939, the present study demonstrated that TRIM37‑induced chemoresistance is partially dependent on the activation of the Wnt/β‑catenin signaling pathway. (spandidos-publications.com)
  • β-catenin is a key molecule in the Wnt/β-catenin signaling pathway and is re-localized to the nucleus and forms a complex with T-cell factor (TCF) to regulate gene expression upon Wnt ligand stimulation ( 15 ). (spandidos-publications.com)
  • Notably, previous studies have demonstrated that TRIM37 may interact with β-catenin and be involved in aberrant activation of the Wnt/β-catenin signaling pathway ( 19 ). (spandidos-publications.com)
  • However, the precise mechanisms underlying the association between TRIM37 and Wnt/β-catenin signaling pathway activation and the potential effect on chemoresistance in OS cells remain to be elucidated. (spandidos-publications.com)
  • [9] Notably, the NBD peptide targets the inflammation induced NF-κB activation pathway sparing the protective functions of basal NF-κB activity allowing for greater therapeutic value and fewer undesired side effects. (wikidoc.org)
  • Numerical computation validated the binding of SFRP1 to WNT1 to suppress Wnt signalling pathway activation in NSCLC. (biomedcentral.com)
  • Reverse of non-small cell lung cancer drug resistance induced by cancer associated fibroblasts via a paracrine pathway. (amedeo.com)
  • A Legionella type IV effector activates the NF-kappaB pathway by phosphorylating the IkappaB family of inhibitors. (semanticscholar.org)
  • One of the most prominent brain areas expressing GC-A is the projection from the medial habenula (MHb) in the epithalamus to the interpeduncular nucleus (IPN) in the midbrain ( Fig. 1 A ). This neural pathway links forebrain limbic areas with midbrain modulatory systems and regulates a diverse array of behaviors including pain, anxiety, sleep, and nicotine addiction ( 14 ⇓ - 16 ). (pnas.org)
  • We identified MLL3 (KMT2C) and MLL4 (KMT2D) as the major H3K4me1 methyltransferases on enhancers ( eLife 2013 ), and CBP and p300 as the H3K27 acetyltransferases in mammalian cells ( EMBO J 2011 ). (nih.gov)
  • This study provides conclusive evidence that the DVL DEP domain is essential for Wnt/β-catenin signaling in mammalian cells and establishes an experimental system suitable for further functional testing of DVL. (asm.org)
  • In particular, high‐resolution quantitative comparative studies in synchronised mammalian cells tracking changes in histone modification during transcriptional activation are currently unavailable. (embopress.org)
  • It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. (creative-biolabs.com)
  • The epigenomic reader Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis. (nih.gov)
  • Modulation was also prevented by an SH3 motif peptide that preferentially binds the SH3 domain of src. (jneurosci.org)
  • therefore looked for binding partners of SH3P2 using a GST-based pull down assay ( 1 ), and found that the protein binds to the class I myosin Myo1E, which has previously been implicated in cell migration ( 4 ). (rupress.org)
  • The proline-rich region of SH3P2 interacts with the SH3 domain of Myo1E, and a C-terminal acidic amino acid cluster of SH3P2 binds to a positively charged region in the TH2 domain of Myo1E's C-terminal tail," Kohno explains. (rupress.org)
  • Hence, HEG1 binds straight to the FHA domains of Rasip1 via a 9 amino acidity (TDVYYSPTS) area of HEG1. (researchensemble.com)
  • Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. (cellsignal.com)
  • When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. (creativebiomart.net)
  • Within macrophages, Mtb exploits a specialized set of metabolic pathways to utilize host-derived nutrients, such as fatty acids and/or cholesterol, for energy production. (prolekare.cz)
  • TLRs are transmembrane receptors in outer or endosomal membranes of immune cells, such as macrophages, dendritic cells, neutrophils, B cells, and NK cells. (jimmunol.org)
  • Their mobility to sites of infection or inflammation is mediated through the emanation of chemotactic substances, such as formylmethionylpeptides, by neutrophils or macrophages at the site of invasion or by activation of serum complement ( 19 ). (pubmedcentralcanada.ca)
  • The present study demonstrated that NLRP3 inflammasome and IL-1β were activated in PMA-induced macrophages in a time-dependent manner, whereas berberine significantly inhibited their expression in a dose-dependent manner in PMA-induced macrophages. (spandidos-publications.com)
  • Monocyte-derived macrophages in late atherogenesis are regarded as primary inflammatory stimuli through either synthesis or secretion of numerous substances, such as interleukin (IL)-1β and −18 ( 1 , 2 ). (spandidos-publications.com)
  • Genome-wide Chromatin Profiling of Legionella pneumophila-Infected Human Macrophages Reveals Activation of the Probacterial Host Factor TNFAIP2. (semanticscholar.org)
  • Enhancers control cell-type-specific gene expression and are critical for cell differentiation and tissue development. (nih.gov)
  • UTX protein, but not its H3K27 demethylase activity, is required for ES cell differentiation and mouse development ( PNAS 2012 ). (nih.gov)
  • MLL4 protein, rather than H3K4me1, controls p300 recruitment to enhancers during ES cell differentiation, suggesting that MLL4 may regulate enhancer activation independent of H3K4me1 ( PNAS 2016 ). (nih.gov)
  • Since LINGO-1 is a leucine-rich repeat protein, which are known for their important role in protein-protein interactions in a wide variety of cellular processes and their implication in important functions like neuronal differentiation and growth or the regulation of axon guidance and regeneration processes, it is logical to deduce that its functions are linked with the nervous system. (wikipedia.org)
  • LINGO-1 also inhibits oligodendrocyte precursor differentiation and myelination, by a mechanism that also involves activation of RhoA, but which apparently does not require p75 or NgR1. (wikipedia.org)
  • Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. (frontiersin.org)
  • Such alterations instruct B cells to undergo immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM), as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. (frontiersin.org)
  • PPAR was initially understood as a regulator of adipocyte differentiation and glucose homeostasis while later on, it became evident that it is also involved in cell differentiation, apoptosis, and angiogenesis, biological processes which are deregulated in cancer. (hindawi.com)
  • It is now established that PPAR ligands can induce cell differentiation and yield early antineoplastic effects in several tumor types. (hindawi.com)
  • We demonstrate the utility of this collection in CD4 + T cell differentiation assays revealing the potential of individual probes to alter multiple T cell subpopulations which may have implications for T cell-mediated processes such as inflammation and immuno-oncology. (nature.com)
  • In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity. (nature.com)
  • The epigenetic state of a cell evolves in an ordered manner during cellular differentiation and epigenetic changes mediate cellular plasticity that enables reprogramming. (nature.com)
  • In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of renal cyst growth. (jci.org)
  • The MLL SET domain is a histone H3 lysine 4-specific methyltransferase whose activity is stimulated with acetylated H3 peptides. (sdbonline.org)
  • The structurally related PR and SET domain containing enzymes (protein lysine methyltransferases (PKMT)) methylate lysine residues on histone "tails", and the dimeric Rossman fold protein arginine methyltransferase (PRMT) enzymes modify arginine. (nature.com)
  • Insulin Acts as a Repressive Factor to Inhibit the Ability of PAR2 to Induce Islet Cell Transdifferentiation. (bioportfolio.com)
  • Recently, we showed that pancreatitis in the context of profound β-cell deficiency was sufficient to induce islet cell transdifferentiation. (bioportfolio.com)
  • This is accomplished by reverse signaling that can induce either cell cycle arrest, or apoptosis in B7-H4 expressing cells (3-5, 9, 10). (novusbio.com)
  • As a result, VTCN1 continues to be hypothesized never to only inhibit traditional T cell activation by APCs within the lymphoid area, but induce T cell tolerance within peripheral focus on cells also. (beloranib.net)
  • Many commonly used CADs, including several cation amphiphilic antihistamines and antidepressants, induce cancer-specific, lysosome-dependent cell death and sensitize cancer cells to chemotherapy. (aacrjournals.org)
  • This frailty can be targeted by cationic amphiphilic drugs (CAD) that induce lysosome-dependent death of cancer cells regardless of their origin, and sensitize them to chemotherapy in vitro and in various murine cancer models in vivo ( 12-19 ). (aacrjournals.org)
  • We're currently trying to identify additional effector molecules that are transported or recruited by Myo1E to induce cell migration," Tanimura says. (rupress.org)
  • In response to ER stress, the cell activates the unfolded protein response (UPR) to restore protein folding homeostasis or induce apoptosis with prolonged ER stress. (mdanderson.org)
  • We found that many of the small molecule inhibitors that we identified require cholesterol for activity. (prolekare.cz)
  • Inhibits activation of caspases. (uniprot.org)
  • We now wanted to uncover the precise molecular mechanism by which SH3P2 inhibits cell motility," Kohno says. (rupress.org)
  • Ex vivo experiments indicate that sevoflurane inhibits platelet and leukocyte activation (n = 5). (asahq.org)
  • The present findings identify platelet-derived soluble TLT-1 as a potent endogenous regulator of sepsis-associated inflammation and open new therapeutic perspectives. (jimmunol.org)
  • PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. (aacrjournals.org)
  • Potent inhibitor of cell death. (uniprot.org)
  • A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. (jimmunol.org)
  • Although crystallographic analyses ( 6 , 7 ) can predict TREM-1 recognition by using Ab-equivalent CDR loops (such as TCRs, CD8, and CTLA-4), its natural ligand has yet to be determined. (jimmunol.org)
  • Similar to other members of the nuclear hormone receptors superfamily, PPAR γ protein has three functional domains: the N-terminal domain, the DNA-binding domain, and a carboxy-terminal ligand-binding pocket (Figure 1 ). (hindawi.com)
  • PPAR γ protein exhibits a structural organization consisting of three functional domains: an N-terminal domain, a DNA-binding domain (DBD) and a carboxy-terminal ligand binding domain (LBD). (hindawi.com)
  • We found that viable neuroblastoma cells and primary tumors are primed for death with tonic sequestration of Bim, a direct activator of apoptosis, by either Bcl-2 or Mcl-1, providing a survival dependency that predicts the activity of Bcl-2 antagonists. (aacrjournals.org)
  • Nascent cancer cells must bypass numerous apoptotic checkpoints that safeguard against oncogenesis ( 1, 2 ), while established cancers encounter therapeutics that interfere with vital functions to activate mitochondrial apoptosis ( 3, 4 ). (aacrjournals.org)
  • Mechanistically, we showed that over-expression of SETDB1 significantly inhibited the apoptosis induced by 5-Fluorouracil in CRC cells, which was closely related to the inhibition of TP53 and BAX expression. (jcancer.org)
  • induces growth arrest or apoptosis depending on the physiological circumstances and cell type. (string-db.org)
  • Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. (string-db.org)
  • apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspase-1. (spandidos-publications.com)
  • Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis , a lack of IKBKG (and hence a lack of active NF-κB) makes cells more prone to apoptosis. (wikidoc.org)
  • In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. (ahajournals.org)
  • The Pro-Apoptosis Bcl-2 Family Antibody Sampler Kit provides an economical means to examine several members of the Bcl-2 family and their activation status. (cellsignal.com)
  • SMYD2 was upregulated in renal epithelial cells and tissues from Pkd1-knockout mice as well as in ADPKD patients. (jci.org)
  • Pkd1 mutant renal epithelial cells and tissues demonstrated increased expression of SMYD2. (jci.org)
  • IL-6 and CXCL2/MIP2 release was much higher in Sigirr- deficient renal myeloid cells but not in Sigirr- deficient tubular epithelial cells after transient hypoxic culture conditions. (jimmunol.org)
  • TLRs are also expressed in nonimmune cells, including kidney tubular epithelial cells and mesangial cells ( 4 ). (jimmunol.org)
  • VTCN1 is an inclusion criterion in 1 clinical trial for malignant ovarian epithelial tumor, of which 1 is open and 0 are closed. (mycancergenome.org)
  • Of the trial that contains VTCN1 status and malignant ovarian epithelial tumor as inclusion criteria, 1 is early phase 1 (1 open) [ 4 ]. (mycancergenome.org)
  • Overexpression of B7-H4 is associated with certain malignancies, including ovarian and breast cancer, which may be a mechanism by which tumor cells suppress T cell immunity and facilitate tumor progression. (thermofisher.com)
  • Further, VTCN1 may be a useful biomarker for the early detection of ovarian cancer and Renal Cell Carcinoma (RCC). (thermofisher.com)
  • A soluble form of B7-H4 is elevated in the serum of ovarian cancer, renal cell carcinoma, and rheumatoid arthritis patients, also in correlation with advanced disease status (13-15). (novusbio.com)
  • Overexpressed in breast, ovarian, endometrial, renal cell (RCC) and non-small-cell lung cancers (NSCLC). (abcam.com)
  • Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. (nih.gov)
  • B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. (nih.gov)
  • The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer. (nih.gov)
  • Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. (aacrjournals.org)
  • We observed increased expression of the prosurvival protein BAG-3 in platinum-resistant ovarian cancer cells. (aacrjournals.org)
  • The heavy chain of PC (41 kDa) consists of the catalytic domain and an activation peptide. (affinitybiologicals.com)
  • B7-H4 is expressed primarily on the membrane of lymphoid cells, and as an immunoinhibitory protein that interacts with receptors on the surface of T lymphocytes, it is involved in mediating cellular and humoral immune responses. (thermofisher.com)
  • Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. (nih.gov)
  • these results suggest that the activation of 5-HT1D receptors selectively enhanced IA via the Gbetagamma of the Go-protein, PKA, and the sequential B-Raf (show SNRPE ELISA Kits )-dependent p38 MAPK (show MAPK14 ELISA Kits ) signaling cascade. (antibodies-online.com)
  • JAKs also have a Src homology 2 (SH2) domain and an N-terminal band four-point-one, ezrin, radixin, moesin (FERM) domain that is critical for mediating the association with cytokine receptors. (thermofisher.com)
  • The RGS domain mediates inhibition of Gα q and Gα i signaling, whereas the amino terminal domain (NTD) directs interaction with adenylyl cyclases, G-protein-coupled receptors, and other signaling partners. (aspetjournals.org)
  • Heterotrimeric G-protein-coupled receptors mediate cell responses to a variety of extracellular ligands ( Ma and Zemmel, 2002 ). (aspetjournals.org)
  • SHM introduces mostly point mutations in variable regions of Ig heavy and light chains, thereby providing the structural substrate for antigen-mediated selection of B cell mutants with higher affinity B cell receptors (BCRs) ( 3 - 5 ). (frontiersin.org)
  • Upon antigen acknowledgement and T cell-APC conjugation, both receptors localize at the center of the immunological synapse (33). (cura-cancer.com)
  • The net contribution of either CD5 and CD6 appears to be inhibitory, considering that cells that absence the receptors are a lot more attentive to antigenic CPI-613 enzyme inhibitor or mitogenic arousal (22, 34). (cura-cancer.com)
  • NRG-1 can bind to 2 receptors: ErbB3 and ErbB4. (ahajournals.org)
  • CD155, CD112, or both are also ligands for the inhibitory receptors TIGIT and CD96 (tactile), which are also expressed on immune cells. (rupress.org)
  • Mature human B7-H4 consists of a 235 amino acid (aa) extracellular domain (ECD) with one Ig-like V-set domain and one Ig-like C2-set domain, a 21 aa transmembrane segment, and a 2 aa cytoplasmic tail (3-5). (novusbio.com)
  • The human LINGO-1 is a single-pass type 1 transmembrane protein of 614 amino acids. (wikipedia.org)
  • It contains a signal sequence of 34 residues, followed by a LRR (leucine-rich repeat) domain, an Ig (immunoglobulin-like) domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. (wikipedia.org)
  • As a transmembrane protein, it can mostly be found on the cell membrane. (wikipedia.org)
  • Cleavage of type III isoforms generates a transmembrane N-terminal fragment ( Figure 1 ). (ahajournals.org)
  • B7-H4 is expressed on activated T-cells, B-cells, monocytes and dendritic cells. (thermofisher.com)
  • We offer oncolytic virus, CAR-T, and dendritic cell related documents, as well as newsletter. (creative-biolabs.com)
  • Expressed on activated T- and B-cells, monocytes and dendritic cells, but not expressed in most normal tissues (at protein level). (abcam.com)
  • Deletion of the ATG 16L1 CTD impairs MHC class II antigen presentation in dendritic cells. (embopress.org)
  • Additionally, clodronate depletion of dendritic cells prevented the aggravated renal failure in Sigirr −/− mice. (jimmunol.org)
  • B7-H4 is a negative co-stimulatory molecule that is expressed on the cell membranes of antigen presenting cells and down-regulates the immune response. (ubc.ca)
  • Unlike classical co-stimulatory molecules (B7-1 and B7-2), whose natural expression and action is strictly limited to antigen-presenting cells (APCs) (11, 12), VTCN1 can be indicated in a number of non-lymphoid organs also, and most significantly, in pancreatic islets (6, Penicillin G Procaine 7, 9, 13-15). (beloranib.net)
  • Here we report a novel chemical rescue approach to identify the metabolic targets of three novel inhibitors, and discovered that cAMP signaling is linked to cholesterol utilization in Mtb. (prolekare.cz)
  • Additionally, the novel inhibitors identified in this study will facilitate evaluation of cholesterol metabolism as a target for chemotherapeutic intervention. (prolekare.cz)
  • In the absence of regulatory subunit IKK-γ the IKK complex is inactive, preventing the downstream signal transduction cascade leading to NF-κB activation. (wikidoc.org)
  • SH3P2 functions as a cytoplasmic anchor for Myo1E… thereby negatively regulating cell motility. (rupress.org)
  • So SH3P2 functions as a cytoplasmic anchor for Myo1E, suppressing its localization to lamellipodial tips and thereby negatively regulating cell motility," Kohno says. (rupress.org)
  • Rasip1 central domains interacts with HEG1 cytoplasmic end. (researchensemble.com)
  • CD5 consists of four tyrosine residues on its cytoplasmic website, that when phosphorylated constitute putative sites for the docking of SH2 domain-containing cytoplasmic molecules. (cura-cancer.com)
  • Open in a separate window Figure 1 CD5 and CD6 are hubs for the assembly of effector enzymes and adaptors(A) CD5 binding partners: CD5 contains in its cytoplasmic tail four tyrosine residues, of which three CPI-613 enzyme inhibitor (Y453, Y465, and Y487) are believed to be phosphorylated upon TCR triggering and can bind the SH2 domains CPI-613 enzyme inhibitor of LCK, RASGAP, CBL, CBLB, SHP1, and PI3K. (cura-cancer.com)
  • B) Compact disc6 binding companions: Compact disc6 contains in its cytoplasmic tail nine tyrosine residues that whenever phosphorylated can dock the SH2 domains of SLP76, TSAD, GADS, GRB2, and SHP1. (cura-cancer.com)
  • Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. (rupress.org)
  • This uniqueness is especially evident in the cytoplasmic domain, which shares little or no homology with other Ig superfamily members. (rupress.org)
  • Furthermore, compound 1 inhibited STAT3 phosphorylation in cells without affecting the total expression of STAT3. (ntu.edu.sg)
  • Phosphorylation of STAT5a is increased in sodium vanadate-treated HEL cells. (thermofisher.com)
  • Further domain mapping of DVL1 showed that both the DVL1 DEP domain and especially its N-terminal region are required and sufficient for Wnt3a-induced phosphorylation of LRP6 and TopFlash reporter activation. (asm.org)
  • There is conclusive evidence showing that DIX domain-mediated DVL polymers, formed in the head-to-tail manner ( 7 ), are a physical platform for the formation of signalosomes, complexes of DVL, and other signaling components that are required for LRP6 phosphorylation ( 8 ). (asm.org)
  • The requirement for the DIX domain for the phosphorylation of LRP6 and its capacity to multimerize seem to be the molecular reason for the absolute requirement for the DIX domain in Wnt/β-catenin signaling. (asm.org)
  • We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. (sciencemag.org)
  • As a total result, silencing Rasip1 reflection in endothelial cells can boost phosphorylation of a Rock and roll base, myosin light string 2 (MLC) (Xu et al. (researchensemble.com)
  • Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). (cellsignal.com)
  • citation needed] The extracellular domain consists of the signal sequence, 11 LRR motifs comprised between an N-terminal and C-terminal capping domains, and the Immunoglobulin-like (IgC2) domain. (wikipedia.org)
  • Moreover, blocking experiments using a TREM-1 fusion protein or using a peptide designed for the CDR3 and the ''F'' β strand of the extracellular domain of TREM-1 have demonstrated a reduced inflammation resulting in improved survival in murine models of endotoxemia and polymicrobial sepsis ( 14 - 16 ). (jimmunol.org)
  • Its small extracellular domain does not bind ligands, and its intracellular domain cannot activate NF-κB because it lacks two essential amino acids (Ser 447 and Tyr 536 ) in the highly conserved TIR domain ( 16 ). (jimmunol.org)
  • TREM-1 is known to cooperate with several TLRs in a synergistic manner ( 8 , 11 , 12 ), whereas TREM-1 silencing downmodulates LPS-induced inflammatory gene activation in myeloid cells ( 13 ). (jimmunol.org)
  • Surprisingly, TLR signaling in intrinsic renal cells predominates in comparison to intrarenal myeloid cells in the postischemic kidney. (jimmunol.org)
  • Renal IR studies with chimeric mice confirmed this finding, as lack of SIGIRR in myeloid cells largely reproduced the phenotype of renal IR injury seen in Sigirr −/− mice. (jimmunol.org)
  • Thus, loss of function mutations in the SIGIRR gene predispose to acute renal failure because SIGIRR prevents overshooting tissue injury by suppressing the postischemic activation of intrarenal myeloid cells. (jimmunol.org)
  • Although the network of intrarenal myeloid cells is considered to significantly contribute to danger signaling in the kidney ( 13 ), studies with Tlr2 - and Tlr4 -chimeric mice propose that TLR2 and TLR4 signaling in renal parenchymal cells predominantly contributes to renal IRI ( 11 , 12 ). (jimmunol.org)
  • We therefore hypothesized that inhibitory factors might suppress TLR signaling specifically in intrarenal myeloid cells during IR. (jimmunol.org)
  • tbx5 is required for Fgf signaling in the limb bud leading to activation of prdm1 expression, which in turn is required for downstream activation of fgf10 expression. (biologists.org)
  • These data suggest a model whereby the stage of the erythroid cell alters the acetylation status of EKLF and plays a critical role in directing its coactivator-corepressor interactions and downstream transcriptional effects. (asm.org)
  • We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)-like motif coupling DNAM-1 to Grb2 and other downstream effectors. (rupress.org)
  • During early development of the nervous system, neurons elongate their axons towards their targets and establish and maintain synapses through formation of cell-cell adhesions. (genome.jp)
  • Cell-cell adhesions also underpin axon-axon contacts and link neurons with supporting schwann cells and oligodendrocytes. (genome.jp)
  • Stimulation of inputs to the bag cell neurons produces an ∼30 min period of depolarization and action potential firing, followed by an ∼18 hr refractory period during which another afterdischarge cannot be elicited. (jneurosci.org)
  • We have also used whole-cell recording to introduce interaction domains into bag cell neurons and observe their effects on cation channel-induced depolarization. (jneurosci.org)
  • During synaptic stimulation, increases ATP availability from mitochondria through regulation of mitochondrial membrane ATP synthase F 1 F 0 activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles. (uniprot.org)
  • PDE2A is richly expressed in the axonal terminals of MHb neurons, and its activation by cGMP depletes cyclic adenosine monophosphates. (pnas.org)
  • We defined the apoptotic set point of neuroblastomas using responses to distinct BH3 death domains providing a BH3 response profile and directly confirmed survival dependencies. (aacrjournals.org)
  • This raises the intriguing possibility that B7-H4 may also regulate β-cell function, stress signaling, and survival independent of immune-regulation. (ubc.ca)
  • With modern, intensive therapy including autologous hematopoietic stem cell transplantation, the median survival is approximately 5 yr. (asnjournals.org)
  • The median survival from diagnosis of patients with symptomatic disease that requires therapy is approximately 5 yr-an increase from 3 yr or so a decade ago, likely a result of widespread application of high-dosage chemotherapy with hematopoietic stem cell transplantation (HSCT) and new drugs. (asnjournals.org)
  • In recent years, lysosomes have emerged as important signaling platforms that regulate cell metabolism, ion homeostasis, motility, and survival in response to the metabolic status of the cell ( 1-4 ). (aacrjournals.org)
  • In particular, bevacizumab an antibody to VEGF-A and the PARP inhibitors show promise in extending overall survival from this disease. (omicsonline.org)
  • It has been suggested that LINGO-1 antagonists such as BIIB033 could significantly improve and regulate survival after neural injury caused by the protein. (wikipedia.org)
  • Whereas early or late LR17 treatment of septic mice improves survival, treml-1 −/− animals are highly susceptible to polymicrobial infection. (jimmunol.org)
  • The CD276 expression helped distinguish survival curves in the test data set. (cdc.gov)
  • [9] ABC lymphoma also has the lowest survival rate compared to DLBCL subtypes, Germinal Center B-cell -like and Undefined Type 3 lymphoma, highlighting the great clinical need to define targets for cancer therapy. (wikidoc.org)
  • BAG-1, BAG-3, and BAG-4 [also known as silencer of death domain (SODD)] are involved in the survival of cancer cells and have been linked with aggressiveness of breast, gastric, and pancreatic cancer ( 8 - 11 ). (aacrjournals.org)
  • Initially, the search for the mechanisms behind these observations focused mainly on the effects of NRG-1 on cardiomyocyte growth and survival and revealed that NRG-1 has Akt-dependent antiapoptotic effects in cultured cardiomyocytes. (ahajournals.org)
  • [1-4] The JAK-STAT pathways are up-regulated by a vast array of cytokines/growth factors. (thermofisher.com)
  • Abnormal constitutive activation of JAK-STAT pathways has been implicated in various cancers and immune disorders. (thermofisher.com)
  • Inhibitors of JAK-STAT pathways are currently being developed in the areas of oncology and immune disorders. (thermofisher.com)
  • The triggering of these pathways ultimately leads to the activation of the transcription factor NF-κB. (jimmunol.org)
  • We anticipate soluble TLT-1 to be important in regulating leukocyte activation during other noninfectious inflammatory disorders. (jimmunol.org)
  • More specifically, we focus on information from recent genome-wide association studies of rheumatoid arthritis, ankylosing spondylitis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and inflammatory bowel disease. (beds.ac.uk)
  • Activated caspase-1 induces secretion of proinflammatory cytokines IL-1β and -18, but also regulates metabolic enzyme expression, phagosome maturation, vasodilation, and pyroptosis, an inflammatory programmed cell death. (cellsignal.com)
  • Furthermore, expression of NtmybB repressed the transcriptional activation mediated by NtmybA2. (plantcell.org)
  • Here, we describe the development of Light-Inducible Transcriptional Effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain 12 - 14 with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana . (pubmedcentralcanada.ca)
  • suggesting B7-H4 is important in the fine tuning of the T-cell mediated immune response. (thermofisher.com)
  • Soluble B7‑H4 functions as a decoy molecule that blocks the inhibitory influence of B7‑H4 on immune activation (15). (novusbio.com)
  • Our discussion then bridges the various aspects of immune dysfunction seen in cancer with the presence of coinhibitory (ex: PD-1, PD-L1, CTLA-4, BTLA) and costimulatory (ex: CD28, ICOS, 4-1BB, CD40, OX40, CD27) signaling. (nih.gov)
  • It is becoming increasingly evident that ischemia-reperfusion (IR) 4 activates innate immune elements that enhance the subsequent tissue injury ( 1 ). (jimmunol.org)
  • How does ischemia translate into innate immune activation? (jimmunol.org)
  • nevertheless, the impact that CD6 and CD5 possess on T cell development and T cell-mediated immune responses could be different. (cura-cancer.com)
  • They may be involved in the organization of cell surface MEMBRANE MICRODOMAINS that regulate the activation of LEUKOCYTES. (bioportfolio.com)
  • Immunofluorescent staining of human cell line MCF7 shows localization to plasma membrane & cell junctions. (bio-connect.nl)
  • Cell membrane. (abcam.com)
  • Subsequently, we define a general mechanism of a progressive loss of VTCN1-mediated negative co-stimulation, which occurs in multiple tissues/cells (islet endocrine cells and APCs) due to the NRD1-dependent diminishment of membrane VTCN1. (beloranib.net)
  • The cancer-associated changes in lysosomal composition result in reduced lysosomal membrane stability, thereby sensitizing cells to lysosome-dependent cell death ( 11 ). (aacrjournals.org)
  • Since the tetramer has a very large surface area into the cell membrane, it is thought that this may serve as an efficient and stable binding platform, facilitating the interaction with NgR, p75, TROY complex. (wikipedia.org)
  • Ligase complex component ATG 16L1 is required for LC 3 lipidation of double‐membrane autophagsomes and of single membranes during phagocytosis and influenza infection, but only single membrane lipidation depends on ATG 16L1's C‐terminal WD 40 domain. (embopress.org)
  • Angiogenesis involves the proteolytic degradation of the basement membrane on which endothelial cells reside followed by the subsequent chemotactic migration and mitosis of these cells to support sustained growth of a new capillary shoot. (google.es)
  • These data suggest that the cation channel-PKC association may require SH3 domain-mediated interactions to bring about modulation, promote membrane depolarization, and initiate prolonged changes in bag cell neuron excitability. (jneurosci.org)
  • The endoplasmic reticulum (ER) is a central membrane-bound organelle constructed from a dynamic network of tubules involved in cellular processes such as protein synthesis, gluconeogenesis, lipid synthesis and processing, and calcium storage and release in the cell and contributes to the generation of autophagosomes and peroxisomes [ 1 ]. (intechopen.com)
  • RER has appeared in all cells and its density is higher, similar to that of the Golgi apparatus and nucleus because in all cells the nascent polypeptide is cotranslationally inserted into their membranes from the ER membrane. (intechopen.com)
  • Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. (uniprot.org)
  • The motor protein's TH1 domain can bind to plasma membrane phospholipids, thereby linking the plasma membrane to the actin cytoskeleton to generate mechanical tension ( 6 ). (rupress.org)
  • Background: Lamins are nuclear membrane structural components that are important in maintaining normal cell functions, such as cell cycle control, DNA replication, and chromatin organization (1-3). (cellsignal.com)
  • Consequently, the distinctive mix of T cell co-inhibitory function with manifestation on Penicillin G Procaine islet cells distinctively positions VTCN1 in the user interface of pancreatic islets as Penicillin G Procaine well as the disease fighting capability. (beloranib.net)
  • The inhibitory activity of PCI is stimulated approximately 10 fold by heparin 1-3 . (affinitybiologicals.com)
  • B7-H4 (B7x, VTCN1) a costimulatory protein which is reported to function as a negative regulator of T-cell mediated immunity. (thermofisher.com)
  • The underlying pathophysiologic phenomena of the clinical features include suppression of humoral- and cell-mediated immunity, elevation of IL-6, abnormalities of the bone marrow microenvironment, and increased osteoclastic activity. (asnjournals.org)
  • Mitogens promote embryonic vascular development, growth, repair and angiogenesis in these cells. (google.es)
  • Applications Tested: This H74 antibody has been tested by flow cytometric analysis of transient hB7-H4 transfected cells. (thermofisher.com)
  • A test is defined as the amount (µg) of antibody that will stain a cell sample in a final volume of 100 µL. (thermofisher.com)
  • The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-VTCN1 antibody linked to 41BB and CD3ζ signaling domains. (creative-biolabs.com)
  • Cells were stained with an STAT4 Abfinity recombinant rabbit monoclonal antibody (Product # 700185 , black histogram) or left unstained (blue histogram). (thermofisher.com)
  • ibody for 1 hour on ice, the cells were stained with a Alexa Fluor 488-conjugated goat anti-rabbit IgG secondary antibody. (thermofisher.com)
  • Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. (frontiersin.org)
  • These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. (frontiersin.org)
  • Affinity's Protein C Paired Antibody Set consists of matched capture and detecting antibodies that have been titrated and optimized for use in sandwich style ELISA assays. (affinitybiologicals.com)
  • This Protein C Paired Antibody Set is intended to facilitate the end user in establishing an "in-house" immunoassay for research purposes only and must not be used for diagnostic applications. (affinitybiologicals.com)
  • Methods and compositions for treatment of cancer with the antibody anti-EGFR mAb806 in combination or series with a src inhibitor or src inhibitors are described. (google.es)
  • 1 . A method of treating cancer in a mammal comprising administering to said mammal a src inhibitor and anti-EGFR antibody, wherein said src inhibitor and anti-EGFR antibody are administered simultaneously, in combination, or one after another series. (google.es)
  • 2 . The method of claim 1 wherein the anti-EGFR antibody is an antibody which recognizes an EGFR epitope which is found in tumorigenic, hyperproliferative or abnormal cells and not detectable in normal cells. (google.es)
  • 5 . The method of claim 1 wherein the src inhibitor is dasatinib and the anti-EGFR antibody is mAb806. (google.es)
  • 7 . A method for blocking or reducing tumor growth of an EGFR-mediated cancer in a mammal comprising administering to said mammal a src inhibitor and anti-EGFR antibody, wherein said src inhibitor and anti-EGFR antibody are administered simultaneously, in combination, or one after another in series. (google.es)
  • 11 . The method of claim 7 wherein the src inhibitor is dasatinib and the anti-EGFR antibody is mAb806 or an active fragment thereof. (google.es)
  • Additionally, targeting IL-1β with a monoclonal antibody can impede the progression of atherosclerosis in ApoE −/− mice ( 4 ). (spandidos-publications.com)
  • 2011). To check out whether HEG1 is normally included in controlling 1 integrin account activation as well, we silenced HEG1 or Rasip1 reflection in HUVEC and sized the presenting of 9EG7 monoclonal antibody as a news reporter of 1 integrin account activation (Lenter et al. (researchensemble.com)
  • To visualize cells expressing myc-tagged dominant-negative constructs, an anti-myc antibody (9E10, Sigma, St. Louis, MO) was used, followed by incubation with a fluorescent secondary antibody (goat anti-mouse IgG AlexaFluor594, Invitrogen). (jneurosci.org)
  • Since its emergence for the first time in 1940, the epigenetic field is witnessing a continuous surge over the last decades [ 1 ]. (biomedcentral.com)
  • This review examines and discusses the involvement and the role of various epigenetic players throughout the different viral life cycle stages and highlights their potential implications in the clinical management of several viral infections, especially human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV), in addition to hepatitis viruses, herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV). (biomedcentral.com)
  • Epigenetic marks would be attractive targets for new therapeutics for autoimmune and allergic diseases, and B cell malignancies. (frontiersin.org)
  • Epigenetic changes brought about by genetic susceptibility and/or environmental exposure can modulate gene expression and alter cellular functions without altering genomic sequences ( 1 ). (frontiersin.org)
  • This study performed a meta-analysis of reprogrammed NSCLC cell lines instead of the direct examination of epigenetic therapy treatment to identify epigenetic therapy targets. (biomedcentral.com)
  • The meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC. (biomedcentral.com)
  • Thus, alternative strategies to direct in vitro experiments for epigenetic therapy such as the investigation of reprogrammed cancer cell lines are required to investigate the effect of epigenetic therapy in NSCLC. (biomedcentral.com)
  • Thus, a detailed and extensive comparative study might indirectly identify the effect of epigenetic therapy in NSCLC cell lines. (biomedcentral.com)
  • Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell carcinoma. (nih.gov)
  • SIGIRR deficiency aggravated postischemic acute renal failure in association with increased renal CXCL2/MIP2, CCL2/MCP-1, and IL-6 mRNA expression 24 h after IR. (jimmunol.org)
  • Cell invasion is attributed to the synthesis and secretion of proteolytically active matrix-metalloproteinases (MMPs) by tumor cells to degrade extracellular matrix (ECM) and promote metastasis. (bioportfolio.com)
  • Of note, various tumor cells have up-regulated levels of B7-H4, which has been linked to metabolic and anti-apoptotic effects. (ubc.ca)
  • My lab utilizes cutting-edge cell editing technology, synthetic biology and chemical biology to understand mutations role in disease and to better understand key genetic nodal points for translational innovation. (case.edu)
  • 5 NRG-1 biology is complicated by the fact that multiple splice variants are produced from the NRG-1 gene (for review, see elsewhere 6 ). (ahajournals.org)
  • 3. A purified protein fragment which is an intracellular portion of a human KDR protein, comprising from about amino acid 790 to about amino acid 1356 as set forth in SEQ ID NO: 2, wherein position 772 is an alanine residue, position 787 is an arginine residue, position 835 is a lysine residue, position 848 is a valine residue and position 1347 is a serine residue. (google.es)
  • a Phylogenetic trees of human PR and SET domain lysine methyltransferases (upper tree), and the β-barrel fold enzymes (lower tree). (nature.com)
  • The persistence of autoreactive T cell responses during T1D prompted several experimental attempts to alleviate diabetogenic autoimmunity artificial enrichment of VTCN1-mediated co-inhibition. (beloranib.net)
  • Inhibition of NFPC function in developing retinal ganglion cells (RGCs) severely reduces axon initiation and elongation and suppresses dendrite genesis. (jneurosci.org)
  • The activation of PC is associated with the release of a small activation peptide (2-3 kDa, called Protein C peptide, or PCP) from the N-terminal of the heavy chain. (affinitybiologicals.com)
  • Synergids secrete peptide signals that lure the tube, while the role of the gametic cells is unknown. (plantcell.org)
  • Together, our findings provide a classification system that identifies tumors with clinical responses to Bcl-2 antagonists, defines Mcl-1 as the principal mediator of Bcl-2 antagonist resistance at diagnosis, and isolates the therapy resistant phenotype to the mitochondria. (aacrjournals.org)
  • Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with comparable potency to the well-known STAT3 inhibitor S3I-201. (ntu.edu.sg)
  • G1/S-phase-specific transcription is regulated by mechanisms involving the E2F/DP heterodimeric transcription factors in animal cells ( Black and Azizkhan-Clifford, 1999 ). (plantcell.org)
  • Here, we identified CCG BINDING PROTEIN1 (CBP1) and demonstrated that it interacts with CCG, Mediator subunits, RNA polymerase II (Pol II), and central cell-specific AGAMOUS-like transcription factors. (plantcell.org)
  • Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. (string-db.org)
  • Addressing molecular mechanisms involved, we find that Huntingtin‐interacting protein HYPB/Setd2 is responsible for virtually all global and transcription‐dependent H3K36 trimethylation, but not H3K36‐mono‐ or dimethylation, in these cells. (embopress.org)
  • SET-domain bacterial effectors target heterochromatin protein 1 to activate host rDNA transcription. (semanticscholar.org)
  • 2. A purified protein fragment which is an intracellular portion of a human KDR protein, comprising from about amino acid 790 to about amino acid 1356 as set forth in SEQ ID NO: 2, wherein position 848 is a valine residue. (google.es)
  • It is speculated that the costimulatory regulation of T cells by B7S1 is influenced by the activation status of B cells. (thermofisher.com)
  • Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. (wikipedia.org)
  • The LINGO-1 structure has been shown to be highly stable both in its crystal form and in solution, thanks to its leucine-rich repeat Ig-composite fold. (wikipedia.org)
  • PP2C (pleckstrin homology domain leucine-rich repeat protein phosphatase) belongs to a novel PP2C-type phosphatase family, the PPM subfamily. (hindawi.com)
  • A1BG is the official symbol for GeneID: 1, "A1BG alpha-1-B glycoprotein [ Homo sapiens ]", in the National Center for Biotechnology Information (NCBI) gene database for gene-specific information. (wikiversity.org)
  • Better understanding of the molecular interactions that influence β-cell function and stress signaling may therefore identify therapeutic targets to protect endogenous β-cells or transplanted islet grafts. (ubc.ca)
  • Some AIDs are organ specific (for example, type 1 diabetes (T1D) targets the pancreas, autoimmune thyroid disease (AITD) attacks the thyroid gland), whereas others can affect multiple organs and/or be associated with systemic manifestations. (beds.ac.uk)
  • A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. (cellsignal.com)
  • Although it is part of the Ig superfamily, DNAM-1 is rather unique. (rupress.org)
  • Additionally, over-expression in mouse islets shielded them from T cell-induced harm in transplantation tests (20), while -cell-specific over-expression shielded against diabetes induced by both Compact disc8+ and Compact disc4+ islet-specific clonal T cells (9, 21). (beloranib.net)
  • [8] Additionally, NF-κB activation was suppressed in HeLa cells after incubation with NBD wild type peptides. (wikidoc.org)
  • The primary inhibitor of APC activity in plasma is Protein C Inhibitor (PCI, also called Plasminogen Activator Inhibitor-3, PAI-3) and to a lesser extent by α1antitrypsin and α2macroglobulin. (affinitybiologicals.com)
  • The effect of sevoflurane on platelet activation, PNC formation and sequestration, cytokine release, and liver damage (alanine aminotransferase release) was analyzed using flow cytometry, luminometry, and immunofluorescence. (asahq.org)
  • Herein, the mechanism by which DNAM-1 controls NK cell-mediated cytotoxicity and cytokine production was elucidated. (rupress.org)
  • Vascular endothelial cells form a luminal non-thrombogenic monolayer throughout the vascular system. (google.es)
  • One class of mitogens selective for vascular endothelial cells include vascular endothelial growth factor (referred to as VEGF or VEGF-A) and the homologues placenta growth factor (PlGF), VEGF-B and VEGF-C. (google.es)
  • As defined above, during junction set up, Rasip1 was hired to endothelial cell-cell connections. (researchensemble.com)
  • Methylations on K4 and K36 of histone H3 (H3K4 and H3K36) correlate with gene activation, whereas methylations on K9 and K27 of histone H3 (H3K9 and H3K27) correlate with gene repression. (nih.gov)
  • Notwithstanding this probably artifactual contribution to activation determined by the experimental design, it is also possible the kinases may actually contribute to positive signaling via CD5 and CD6 in very defined contexts, therefore explaining the dual function that has been many times attributed to CD6 and occasionally to CD5. (cura-cancer.com)
  • PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. (cellsignal.com)
  • It also promoted activation of kinases Erk and Akt, and calcium fluxes. (rupress.org)
  • Bcl-2 and Mcl-1) can bind activator BH3′s preventing Bak or Bax activation and providing a buffer against cell death. (aacrjournals.org)
  • In 1990, Ellington and Szostak [ 1 ], in the context of their studies on self-splicing group I introns and ribozymes, reported on the production and characterization of short, random RNA sequences able to bind specifically to one of various organic dyes used as target. (mdpi.com)
  • Myo1E's localization to lamellipodia was mediated by the protein's TH2 domain, which can bind to newly polymerized F-actin ( 5 ). (rupress.org)
  • Hence, the region of Rasip1 encompassing the FHA domain is both sufficient and required to bind to HEG1. (researchensemble.com)
  • Domains that may have a role in MLL function include the AT hooks, which bind DNA, a region homologous to DNA methyl transferases (DNMT), the cysteine-rich PHD domain, and a highly conserved SET domain. (sdbonline.org)
  • ErbB2 cannot directly bind NRG-1, but it is the favored partner for heterodimerization. (ahajournals.org)
  • This function was reportedly dependent on the ability of DNAM-1 to bind in cis to integrin LFA-1. (rupress.org)
  • NF-protocadherin (NFPC)-mediated cell-cell adhesion plays a critical role in vertebrate neural tube formation. (jneurosci.org)
  • Nervous system development requires the coordinated regulation of cellular interactions, which are mediated through cell adhesion molecules, including the cadherins. (jneurosci.org)
  • Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. (rupress.org)
  • B ) qRT-PCR analysis of relative Smyd2 mRNA expression in WT, Null, PH2, and PN24 cells. (jci.org)
  • Interestingly, pancreatic β-cells also express high levels of B7-H4 mRNA and moderate levels of B7-H4 protein. (ubc.ca)
  • LINGO-1 mRNA is expressed in an almost exclusive manner in the central nervous system during both embryonic and postnatal stages. (wikipedia.org)
  • In this study, we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocyte activation and modulating platelet-neutrophil crosstalk. (jimmunol.org)
  • Hence, in infected tissues TLR activation fosters the production of proinflammatory cytokines, chemokines, and other soluble mediators that set up local inflammation. (jimmunol.org)
  • May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity). (uniprot.org)
  • The nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3) inflammasome has recently emerged as a pivotal regulator of chronic inflammation. (spandidos-publications.com)
  • The NLRP3 inflammasome has been demonstrated to be associated with chronic inflammation, resulting in IL-1β and IL-18 maturation ( 5 ). (spandidos-publications.com)
  • One way in which these "danger" signals trigger inflammation is through activation of inflammasomes, which are multiprotein complexes that assemble in the cytosol after exposure to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) and result in the activation of caspase-1 and subsequent cleavage of proinflammatory cytokines IL-1β and IL-18 (Reviewd in 1-6). (cellsignal.com)