CCAAT-Enhancer-Binding Protein-alpha
A CCAAT-enhancer-binding protein found in LIVER; ADIPOSE TISSUE; INTESTINES; LUNG; ADRENAL GLANDS; PLACENTA; OVARY and peripheral blood mononuclear cells (LEUKOCYTES, MONONUCLEAR). Experiments with knock-out mice have demonstrated that CCAAT-enhancer binding protein-alpha is essential for the functioning and differentiation of HEPATOCYTES and ADIPOCYTES.
CCAAT-Enhancer-Binding Proteins
A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
CCAAT-Enhancer-Binding Protein-beta
A CCAAT-enhancer-binding protein found in LIVER; INTESTINES; LUNG and ADIPOSE TISSUE. It is an important mediator of INTERLEUKIN-6 signaling.
CCAAT-Enhancer-Binding Protein-delta
A member of the C-EBP protein family of transcription factors. It plays a key role in G0 PHASE mammary EPITHELIAL CELL growth arrest, and it is involved in transcriptional regulation of INTERLEUKIN 1; INTERLEUKIN 6; and TUMOR NECROSIS FACTOR-ALPHA.
Enhancer Elements, Genetic
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
Promoter Regions, Genetic
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
DNA-Binding Proteins
Transcription Factors
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Nuclear Proteins
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Transcription Factor CHOP
Gene Expression Regulation
Base Sequence
Adipocytes
Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.
Transcription, Genetic
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Adipogenesis
The differentiation of pre-adipocytes into mature ADIPOCYTES.
Cell Differentiation
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Binding Sites
Transcriptional Activation
Electrophoretic Mobility Shift Assay
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
3T3-L1 Cells
Protein Binding
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Response Elements
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
Transfection
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Cells, Cultured
Granulocytes
Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.
Cell Nucleus
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
3T3 Cells
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
PPAR gamma
Myelopoiesis
Formation of MYELOID CELLS from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via MYELOID STEM CELLS. Myelopoiesis generally refers to the production of leukocytes in blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the lymphoid tissue.
Gene Expression
Liver
Down-Regulation
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Chromatin Immunoprecipitation
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
Genes, Reporter
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Trans-Activators
Leucine Zippers
DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.
Adipose Tissue
Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.
Luciferases
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Endrin
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Blotting, Western
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
DNA
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Up-Regulation
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Tumor Cells, Cultured
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Gene Expression Regulation, Enzymologic
Mutation
Regulatory Sequences, Nucleic Acid
Hepatocyte Nuclear Factor 3-beta
DNA Primers
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Acute-Phase Reaction
An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma.
NF-kappa B p50 Subunit
A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p105 precursor protein and is capable of forming dimeric complexes with itself or with TRANSCRIPTION FACTOR RELA. It regulates expression of GENES involved in immune and inflammatory responses.
Protein Isoforms
RNA Polymerase Sigma 54
Cyclic AMP Response Element-Binding Protein
HeLa Cells
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Reverse Transcriptase Polymerase Chain Reaction
U937 Cells
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
Mice, Transgenic
Transcription Factor AP-2
A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Carrier Proteins
Transport proteins that carry specific substances in the blood or across cell membranes.
NF-kappa B
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Mice, Inbred C57BL
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Oligonucleotides
Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)
Receptors, Cytoplasmic and Nuclear
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
Phosphorylation
Glucocorticoids
A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.
Blotting, Northern
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Gene Expression Regulation, Leukemic
Leukemia, Myeloid, Acute
Transcription Factor AP-1
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
Recombinant Fusion Proteins
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Endoplasmic Reticulum Stress
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
RNA, Small Interfering
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Epithelial Cells
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Gene Expression Regulation, Neoplastic
Mutagenesis, Site-Directed
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
HL-60 Cells
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Hepatocytes
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Interleukin-6
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
Monocyte-Macrophage Precursor Cells
Parent cells in the lineage that gives rise to MONOCYTES and MACROPHAGES.
Repressor Proteins
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Immunohistochemistry
Lipopolysaccharides
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Endoplasmic Reticulum
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Monosaccharide Transport Proteins
A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.
Cell Proliferation
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Proto-Oncogene Proteins
Plasmids
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Gene Expression Profiling
Poly(A)-Binding Proteins
Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.
Fatty Acid-Binding Proteins
Deoxyribonuclease I
An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.
Cell Division
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Fibroblasts
Macrophages
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Phenotype
Rats, Sprague-Dawley
Inflammation
Oligonucleotide Array Sequence Analysis
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Hypertonic Solutions
Proteins
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
DNA Footprinting
A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Liver Neoplasms
Tumors or cancer of the LIVER.
Insulin
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Recombinant Proteins
Proteins prepared by recombinant DNA technology.
Sterol Regulatory Element Binding Protein 1
Gene Expression Regulation, Developmental
CCAAT-Binding Factor
Chloramphenicol O-Acetyltransferase
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
Dimerization
Keratinocytes
Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Myxococcus xanthus
Consensus Sequence
A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.
Homeodomain Proteins
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
NFATC Transcription Factors
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
Cyclic AMP
Sp1 Transcription Factor
Lymphoid Enhancer-Binding Factor 1
Tacrolimus Binding Proteins
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
Gene Knockdown Techniques
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Tumor Necrosis Factor-alpha
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.
Core Binding Factor Alpha 2 Subunit
Cell Cycle
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Histone Deacetylase 1
Interleukin-1beta
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
Poly(A)-Binding Protein I
A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.
Enzyme Inhibitors
RNA-Binding Proteins
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
NIH 3T3 Cells
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Nuclear Factor 90 Proteins
A family of double-stranded RNA-binding proteins that are related to NFATC TRANSCRIPTION FACTORS. In addition to binding to RNA, nuclear factor 90 proteins form heterodimeric complexes that regulate GENETIC TRANSCRIPTION and may play a role in T-CELL activation.
Mutagenesis
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
MEF2 Transcription Factors
Activating transcription factors of the MADS family which bind a specific sequence element (MEF2 element) in many muscle-specific genes and are involved in skeletal and cardiac myogenesis, neuronal differentiation and survival/apoptosis.
Insulin-Like Growth Factor Binding Proteins
A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)
Stromal Cells
Unfolded Protein Response
A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.
Neoplasm Proteins
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Myogenic Regulatory Factors
A family of muscle-specific transcription factors which bind to DNA in control regions and thus regulate myogenesis. All members of this family contain a conserved helix-loop-helix motif which is homologous to the myc family proteins. These factors are only found in skeletal muscle. Members include the myoD protein (MYOD PROTEIN); MYOGENIN; myf-5, and myf-6 (also called MRF4 or herculin).
Protein Biosynthesis
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Genes, Regulator
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
Leptin
A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.
Receptors, TNF-Related Apoptosis-Inducing Ligand
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
RNA Interference
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Immunoblotting
Sequence Homology, Nucleic Acid
Hematopoiesis
The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
Models, Biological
Stem Cells
Membrane Proteins
Isoenzymes
Proto-Oncogene Proteins c-jun
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.
Restriction Mapping
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Sequence Homology, Amino Acid
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Heat-Shock Proteins
TATA Box
Chromatin
Introns
Oligodeoxyribonucleotides
Sequence Alignment
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Leukemia, Myeloid
HIV Enhancer
Cis-acting regulatory sequences in the HIV long terminal repeat (LTR) which play a major role in induction or augmentation of HIV gene expression in response to environmental stimuli such as mitogens, phorbol esters, or other viruses. The HIV enhancer is the binding site for many cellular transcription factors including the nuclear factor NF-kappa B.
Poly(A)-Binding Protein II
A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.
Kidney
Osmolar Concentration
Organ Specificity
Bone Marrow Cells
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Gene Expression Regulation, Bacterial
Oligonucleotide Probes
Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.
Gene Expression Regulation, Viral
DNA, Complementary
Conserved Sequence
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Core Binding Factor alpha Subunits
A family of transcription factors that bind to the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. Family members contain a highly conserved DNA-binding domain known as the runt domain. They can act as both activators and repressors of expression of GENES involved in CELL DIFFERENTIATION and CELL CYCLE progression.
Insulin-Like Growth Factor Binding Protein 3
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
Calcium-Binding Proteins
Drosophila Proteins
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Repetitive Sequences, Nucleic Acid
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Periplasmic Binding Proteins
Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.
COS Cells
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
CREB-Binding Protein
A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.
Y-Box-Binding Protein 1
Chickens
Exons
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Tacrolimus Binding Protein 1A
Globins
A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.