An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
An ACYCLOVIR analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.
A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.
A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.
A pyrimidine nucleoside formed in the body by the deamination of CYTARABINE.
The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Agents that inhibit PROTEIN KINASES.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Established cell cultures that have the potential to propagate indefinitely.
Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
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.
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.
2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The functional hereditary units of VIRUSES.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
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.
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.
Genes that are used transgenically, i.e., via GENE TRANSFER TECHNIQUES to induce CELL DEATH.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The rate dynamics in chemical or physical systems.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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 introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
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).
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.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
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.
An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
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.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
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.
Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.
A purine or pyrimidine base bonded to DEOXYRIBOSE.
An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. Subfamilies, based on biological characteristics, include: ALPHAHERPESVIRINAE; BETAHERPESVIRINAE; and GAMMAHERPESVIRINAE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
An enzyme that catalyzes the phosphorylation of uridine and cytidine to uridine 5'-phosphate and cytidine 5'-phosphate, respectively. ATP, dUTP, dGTP, and dATP are effective phosphate donors. EC 2.7.1.48.
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.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Proteins prepared by recombinant DNA technology.
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.
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.
Deoxyribonucleic acid that makes up the genetic material of viruses.
A folic acid derivative used as a rodenticide that has been shown to be teratogenic.
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
A cell line derived from cultured tumor cells.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
Elements of limited time intervals, contributing to particular results or situations.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
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.
The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans.
The process by which a DNA molecule is duplicated.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
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 group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)
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.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
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.
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
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)
Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)
The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.
Proteins found in any species of virus.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Change brought about to an organisms genetic composition by unidirectional transfer (TRANSFECTION; TRANSDUCTION, GENETIC; CONJUGATION, GENETIC, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Rare mixed tumors of the brain and rarely the spinal cord which contain malignant neuroectodermal (glial) and mesenchymal components, including spindle-shaped fibrosarcoma cells. These tumors are highly aggressive and present primarily in adults as rapidly expanding mass lesions. They may arise in tissue that has been previously irradiated. (From Br J Neurosurg 1995 Apr;9(2):171-8)
A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
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 intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
An experimental lymphocytic leukemia of mice.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
5-Bromo-2'-deoxycytidine. Can be incorporated into DNA in the presence of DNA polymerase, replacing dCTP.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A class of organic compounds containing two ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The sum of the weight of all the atoms in a molecule.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Transport proteins that carry specific substances in the blood or across cell membranes.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
An enzyme that catalyzes the hydrolytic deamination of deoxycytidylic acid to deoxyuridylic acid and ammonia. It plays an important role in the regulation of the pool of deoxynucleotides in higher organisms. The enzyme also acts on some 5-substituted deoxycytidylic acids. EC 3.5.4.12.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.

Transduction of glioma cells using a high-titer retroviral vector system and their subsequent migration in brain tumors. (1/2453)

The intracranial migration of transduced glioma cells was investigated in order to improve the treatment of malignant glioma by gene therapy using retroviral vectors. In this study, about half the volume of the tumor mass could be transduced in 14 days after only a single implantation of 3 x 10(5) retrovirus-producing cells into a tumor mass with a diameter of 5 mm. Moreover, we were able to follow the migration of glioma cells transduced by the lacZ-harboring retroviruses originating from the high-titer retrovirus-producing cells. Besides the importance of using a high-titer retroviral vector system, our results also indicate that the implantation site of the virus-producing cells and the interval between the implantation of the virus-producing cells and the subsequent administration of ganciclovir are important factors for the efficient killing of glioma cells.  (+info)

Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells. (2/2453)

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.  (+info)

Modulation of the cytotoxicity of 3'-azido-3'-deoxythymidine and methotrexate after transduction of folate receptor cDNA into human cervical carcinoma: identification of a correlation between folate receptor expression and thymidine kinase activity. (3/2453)

Cervical carcinoma is an AIDS-defining illness. The expression of folate receptors (FRs) in cervical carcinoma (HeLa-IU1) cells was modulated by stable transduction of FR cDNA encapsidated in recombinant adeno-associated virus-2 in the sense and antisense orientation (sense and antisense cells, respectively). Although sense cells proliferated slower than antisense or untransduced cells in vivo and in vitro in 2% (but not 10%) FCS, [methyl-3H]thymidine incorporation into DNA was significantly increased in sense cells in 10% serum; therefore, the basis for this discrepancy was investigated. The activity of thymidine kinase (TK) was subsequently directly correlated with the extent of FR expression in single cell-derived clones of transduced cells. This elevated TK activity was not a result of recruitment of the salvage pathway based on the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, persistence of increased thymidine incorporation despite the exogenous provision of excess 5,10-methylene-tetrahydrofolate, and documentation of adequate folates in sense cells. The increase in TK activity conferred significant biological properties to sense cells (but not antisense or untransduced cells) as demonstrated by augmented phosphorylation of 3'-azido-3'-deoxythymidine (AZT) and concomitantly greater sensitivity to the cytotoxic effects of AZT. Conversely, sense cells were highly resistant to methotrexate, but this was reversed by the addition of AZT. The direct correlation of FR expression and TK activity indicates a previously unrecognized consequence of FR overexpression.  (+info)

Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. (4/2453)

Chronic lymphocytic leukemia (CLL) shows a remarkably heterogeneous clinical outcome; survival ranges from several months in advanced stages to more than 10 years in early stages. The Binet and Rai staging systems distinguish three major prognostic subgroups, but do not accurately predict the individual risk of disease progression in early CLL (Binet stage A or Rai stage 0 to II). Because most newly diagnosed CLL patients present with early disease, it seems desirable to search for additional prognostic factors to identify early CLL patients at high risk of rapid progression. It has been shown that elevated serum thymidine kinase (s-TK) levels predict disease progression in CLL. Therefore, this study aimed to assess the prognostic value of s-TK in 122 previously untreated patients with Binet stage A CLL (mean age +/- SD, 58.7 +/- 8.5 years). In univariate analyses, 18 of the 22 parameters investigated predicted progression-free survival (PFS). In a stepwise multiple regression analysis, only three parameters provided independent prognostic information on PFS: s-TK greater than 7.1 U/L; presence of lymphadenopathy; and white blood cell (WBC) count greater than 75, 000/microL. When added to the classification of smoldering versus nonsmoldering CLL, s-TK levels separated two groups within the group of nonsmoldering stage A patients: patients with s-TK values greater than 7.1 U/L had a median PFS of 8 months, whereas patients with s-TK values +info)

Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. (5/2453)

We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.  (+info)

Use of the Gal4-UAS technique for targeted gene expression in the zebrafish. (6/2453)

The most common way to analyze the function of cloned genes in zebrafish is to misexpress the gene product or an altered variant of it by mRNA injection. However, mRNA injection has several disadvantages. The GAL4-UAS system for targeted gene expression allows one to overcome some of these disadvantages. To test the GAL4-UAS system in zebrafish, we generated two different kinds of stable transgenic lines, carrying activator and effector constructs, respectively. In the activator lines the gene for the yeast transcriptional activator GAL4 is under the control of a given promoter, while in the effectors the gene of interest is fused to the sequence of the DNA-binding motif of GAL4 (UAS). Crosses of animals from the activator and effector lines show that effector genes are transcribed with the spatial pattern of the activators. This work smoothes the way for a novel method of misexpression of gene products in zebrafish in order to analyze the function of genes in developmental processes.  (+info)

Staurosporine blocked normal cells at G1/S boundary. (7/2453)

AIM: To reveal the regulating difference of G1/S-phase transition between normal and tumor cells by using staurosporine, an unspecific kinase inhibitor. METHODS: Flow cytometry, Dot blot, kinase activity assay, and electrophoresis. RESULTS: A 18-h treatment with staurosporine (5 micrograms.L-1) blocked normal cell line 2BS cells (normal human embryonic lung fibroblast, 5-20 passages) in G1 phase, decreased their thymidine kinase (TK) mRNA level and activity, and also dephosphorylated an intracellular 107 kDa protein. Meanwhile, all these effects in 2BS cells disappeared only by washing staurosporine away. Such kind of effects did not occur in tumor cell line BGC-823 cells (human stomach cancer cell). CONCLUSION: During the period of G1/S-phase transition, the kinases involved are more sensitive to staurosporine in normal cells than in tumor cells.  (+info)

Intronless mRNA transport elements may affect multiple steps of pre-mRNA processing. (8/2453)

We have reported recently that a small element within the mouse histone H2a-coding region permits efficient cytoplasmic accumulation of intronless beta-globin cDNA transcripts. This sequence lowers the levels of spliced products from intron-containing constructs and can functionally replace Rev and the Rev-responsive element (RRE) in the nuclear export of unspliced HIV-1-related mRNAs. In work reported here, we further investigate the molecular mechanisms by which this element might work. We demonstrate here through both in vivo and in vitro assays that, in addition to promoting mRNA nuclear export, this element acts as a polyadenylation enhancer and as a potent inhibitor of splicing. Surprisingly, two other described intronless mRNA transport elements (from the herpes simplex virus thymidine kinase gene and hepatitis B virus) appear to function in a similar manner. These findings prompt us to suggest that a general feature of intronless mRNA transport elements might be a collection of phenotypes, including the inhibition of splicing and the enhancement of both polyadenylation and mRNA export.  (+info)

TY - JOUR. T1 - Coexpression of herpesviral thymidine kinase reporter gene and VEGF gene for noninvasive monitoring of therapeutic gene transfer. T2 - An in vitro evaluation. AU - Anton, Martina. AU - Wittermann, Constanze. AU - Haubner, Roland. AU - Simoes, Marcus. AU - Reder, Sybille. AU - Essien, Bryan. AU - Wagner, Bettina. AU - Henke, Julia. AU - Erhardt, Wolf. AU - Noll, Steffi. AU - Hackett, Neil R.. AU - Crystal, Ronald G.. AU - Schwaiger, Markus. AU - Gansbacher, Bernd. AU - Bengel, Frank M.. PY - 2004/10/1. Y1 - 2004/10/1. N2 - Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). Methods: Accumulation of 14C-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FIAU) and ...
Toda la información sobre las últimas publicaciones científicas de la Clínica Universidad de Navarra. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model
All information about the latest scientific publications of the Clínica Universidad de Navarra. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model
Abstract We constructed a functional MoMuLV-based bicistronic retroviral vector encoding the herpes simplex virus type I thymidine kinase gene, which induces sensitivity to the prodrug ganciclovir (gcv), and the reporter beta-galactosidase gene (MFG-tk-IRES-lacZ). The U937 histiocytic cell line was transduced with this vector, and a clone (VB71) with high-level transgene expression was selected. Severe combined immunodeficient (SCID) mice were injected with VB71 cells to evaluate the role of long terminal repeat methylation in transgene silencing in vivo and to see whether 5-azacytidine (5 aza-C) demethylating agent prevented it. We found 5 aza-C maintained gene expression at high level in vitro. In vivo, time to tumor onset was significantly longer in SCID mice receiving the VB71 cells, 5 aza-C, and gcv compared with animals treated with either 5 aza-C or gcv alone. The number of injected tumor cells influences tumor onset time and the efficacy of 5 aza-C and gcv treatment. The standard ...
Summary Purified herpes simplex virus thymidine kinase has been used to immunize mice for the production of monoclonal antibodies to the enzyme. Monoclonal antibodies were successfully produced against both herpes simplex virus type 1 and type 2 enzymes. These antibodies should prove useful for detecting the enzyme under a variety of experimental conditions. We also demonstrate that the antibodies can provide an alternative method for obtaining large amounts of purified thymidine kinase.
TY - JOUR. T1 - Stem cells as vectors to deliver HSV/tk gene therapy for malignant gliomas. AU - Rath, Prakash. AU - Shi, Huidong. AU - Maruniak, Joel A.. AU - Litofsky, N. Scott. AU - Maria, Bernard L.. AU - Kirk, Mark D.. PY - 2009/10/12. Y1 - 2009/10/12. N2 - The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not ...
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Summary The induction of thymidine kinase (TK) and DNA polymerase was inhibited by interferon (IFN) in mouse L-cells infected with herpes simplex virus type 1 (HSV-1). The inhibitory activity of IFN at this early stage of HSV-1 replication was followed by a reduced virus yield and was dependent on the multiplicity of infection. The expression of a cloned thymidine kinase (tk) gene of HSV-1, in biochemically transformed L-cells (LTK+), was not affected by IFN. These same LTK+ cells, however, developed an antiviral state since, upon HSV-1 infection, the induction of TK and DNA polymerase of the replicating virus was inhibited by IFN. Furthermore, IFN inhibited the transactivation of the HSV-1 tk gene in the biochemically transformed LTK+ cells, which followed infection by a virus mutant defective in the tk gene (HSV-1 TK-). This transactivation is dependent on expression of immediate-early HSV-1 α-genes. These results indicate that IFN inhibits HSV-1 replication at an early step prior to DNA synthesis.
Thymidine kinases form part of the salvage pathway for pyrimidine deoxyribonucleotide synthesis. TKs are expressed in a variety of organisms from human to bacteria as well as in a number of viruses. The reaction catalysed by TK involves the transfer of a γ-phosphoryl moiety from ATP to 2deoxy-thymidine (dThd) to produce thymidine 5-monophosphate (dTMP). Certain TKs, such as those from herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) have, in addition, thymidylate kinase activity allowing the conversion of dTMP to thymidine 5-diphosphate (dTDP). TKs can be classified into two types which differ in several respects [1]. Type 1 TKs are of higher molecular weight, typically around 40 kDa, and are active as homodimers. This subfamily contains the HSV1, HSV2 and VZV TKs, and also mitochondrial TK.. TKs of type 2 include those from poxviridae such as vaccinia virus (VV) and variola virus, [2], as well as from human [3] hTK, (human type II thymidine kinase 1) and mouse [4]. Type ...
Mammals have two isoenzymes, that are chemically very different, TK1 and TK2. The former was first found in fetal tissue, the second was found to be more abundant in adult tissue, and initially they were termed fetal and adult thymidine kinase. Soon it was shown that TK1 is present in the cytoplasm only in anticipation of cell division (cell cycle-dependent),[10][11] whereas TK2 is located in mitochondria and is cell cycle-independent.[12][13] The two isoenzymes have different reaction kinetics and are inhibited by different inhibitors. The viral thymidine kinases differ completely from the mammalian enzymes both structurally and biochemically and are inhibited by inhibitors that do not inhibit the mammalian enzymes.[14][15][16] The genes of the two human isoenzymes were localized in the mid-1970s.[17][18] The gene for TK1 was cloned and sequenced.[19] The corresponding protein has a molecular weight of about 25 kD. Normally, it occurs in tissue as a dimer with a molecular weight of around 50 ...
Aims: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an important proliferation marker. We explored the association of preoperative serum TK1 activity with clinicopathological parameters and prognosis in terms of recurrence-free survival (RFS) in breast cancer (BC) patients. Patients and methods: TK1 activity in serum of 120 healthy women and 161 BC patients was measured by quantitative ELISA. Results: Serum TK1 activity in BC patients was significantly higher than in healthy women (P , 0.0001). In BC patients elevated TK1 activity was significantly associated with advanced T stage (P = 0.015), higher grade (P = 0.013), presence of tumor necrosis (P = 0.006), vascular invasion (P = 0.002), and lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P = 0.0004 and P = 0.003). Higher TK1 activity was found in patients with BRCA1/2 mutations compared to those without the mutation (P = 0.004). Multivariate Cox proportional hazards analyses demonstrated that ...
TY - JOUR. T1 - Differences in thermostability of thymidine kinase isoenzymes in normal ovary and ovarian carcinoma. AU - Demeter, A.. AU - Abonyi, M.. AU - Look, K. Y.. AU - Keszler, G.. AU - Staub, M.. AU - Weber, G.. PY - 2001/4/17. Y1 - 2001/4/17. N2 - Thymidine kinase I (TK 1 EC. 2.7.1.21) the most specific and cell-cycle regulated salvage enzyme for pyrimidine nucleoside supply of DNA synthesis is a promising target to rationally designed chemo- and other therapies. The present study was undertaken to compare the heat stability of TK isoenzymes of both normal ovarian and epithelial ovarian cancer cells. Tissue extracts of epithelial ovarian carcinomas (N = 7) and normal ovaries (N=9) were analyzed for thymidine kinase activity using the polyethyleneimine-cellulose disc radioassay. The TK activity in extracts of ovarian carcinomas was 12-fold higher than in extracts of normal ovaries. The TK activity of ovarian carcinomas decreased significantly even after 30 minutes incubation at 37°C ...
Two plasmids containing nonoverlapping deletions of the herpes simplex virus thymidine kinase gene were introduced into thymidine kinase-deficient mouse L cells by DNA-mediated gene transfer. Thymidine kinase-producing transformants were generated by a mixture of the two plasmids at a frequency significantly greater than that generated by either plasmid alone. Southern blot analyses demonstrated that functional thymidine kinase genes were generated by homologous recombination between the two deletion mutants. ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacok
TY - JOUR. T1 - Glucocorticoid regulation of the genes encoding thymidine kinase, thymidylate synthase, and ornithine decarboxylase in P1798 cells. AU - Barbour, Karen W.. AU - Berger, Sondra H.. AU - Berger, Franklin G.. AU - Thompson, E. Aubrey. PY - 1988/1. Y1 - 1988/1. N2 - The expression of a number of genes was measured in P1798 cells treated for various periods of time with 0.1 mm dexamethasone. Thymidine kinase (TK) activity decreased under these conditions with 50% inhibition achieved within approximately 8 h. Decreased TK activity was associated with reduced abundance of TK mRNA. Analysis of nuclear tran-scription indicated that this was attributable to a decrease in the number of RNA polymerase II molecules engaged in transcription of the TK gene. With respect to TK, there was an overall correlation between enzyme activity, mRNA, and nuclear transcription. The data are consistent with the hypothesis that glucocorticoid inhibition of expression of TK is primarily due to inhibition of ...
TY - JOUR. T1 - Gene therapy for transplant arteriosclerosis. AU - Rekhter, M. D.. AU - Shah, N.. AU - Simari, R. D.. AU - Work, C.. AU - Kim, J. S.. AU - Nabel, G. J.. AU - Nabel, E. G.. AU - Gordon, D.. PY - 1997/12/1. Y1 - 1997/12/1. N2 - Transplant arteriosclerosis is a thickening of the intima that develops in arteries of transplanted organs. Smooth muscle cell (SMC) replication plays a central role in its pathogenesis. One strategy to selectively eliminate dividing cells is to express a herpesvirus thymidine kinase (tk) gene which phosphorylates the nucleoside analog, ganciclovir, into a toxic form which leads to cell killing. To evaluate a feasibility of transgene expression in arterial grafts, we performed ex vivo adenovirus (ADV)-mediated transfer of human placental alkaline phosphatase (hpAP) gene into aortas of donor rabbits, and then transplanted them into carotid artery of recipient rabbits. 2 days post-transplant luminal endothelial cells, adventitial cells, and medial SMCs ...
Local inflammatory response and vector spread after direct intraprostatic injection of a recombinant adenovirus containing the herpes simplex virus thymidine kinase gene and ganciclovir therapy in mice Academic Article ...
Thymidine kinase converts 5-fluorodeoxyuridine to 5-fluorodeoxyuridine monophosphate, which causes disruption of deoxynucleotide triphosphate ratios. The fission yeast Schizosaccharomyces pombe does not express endogenous thymidine kinase but 5-fluorodeoxyuridine inhibits growth when exogenous thymidine kinase is expressed. Unexpectedly, we found that 5-fluorodeoxyuridine causes S phase arrest even without thymidine kinase expression. DNA damage checkpoint proteins such as the 9-1-1 complex were required for viability in the presence of 5-fluorodeoxyuridine. We also found that strains with circular chromosomes, due to loss of pot1+, which have higher levels of replication stress, were more sensitive to loss of the 9-1-1 complex in the presence of 5-fluorodeoxyuridine. Thus, our results suggest that strains carrying circular chromosomes exhibit a greater dependence on DNA damage checkpoints to ensure viability in the presence of 5-fluorodeoxyuridine compared to stains that have linear ...
DNA containing the herpes simplex virus thymidine kinase (HSVtk) gene was used to transform wild-type tk+ mouse L cells to a tk++ status in vitro using methotrexate as a selective agent. HSVtk DNA was also used to transform mouse bone marrow cells in vitro. Transformed marrow cells injected into irradiated and methotrexate-treated recipient mice gave rise to proliferating cells which in some cases dominated the marrow population and which contained HSVtk gene sequences. ...
Cadee JA, van Luyn MJ, Brouwer LA, Plantinga JA, van Wachem PB, De Groot CJ, den OW, and Hennink WE. (2000). In vivo biocompatibility of dextran-based hydrogels. J Biomed Mater Res 50: 397-404. PubMed. de Vries EF, van WA, Harmsen MC, Mulder NH, Vaalburg W, and Hospers GA. (2000). [(11)C]FMAU and [(18)F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections. Nucl Med Biol 27: 113-9. PubMed. Dijk F, Westerhof M, Busscher HJ, van Luyn MJ, and van Der Mei HC. (2000). In vitro formation of oropharyngeal biofilms on silicone rubber treated with a palladium/tin salt mixture. J Biomed Mater Res 51: 408-12. PubMed. Kas-Deelen AM, de Maar EF, Harmsen MC, Driessen C, van Son WJ, and The TH. (2000). Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection: effect of acute rejection. J Infect Dis 181: 721-4. PubMed. Kas-Deelen AM, Harmsen MC, de Maar EF, Oost-Kort WW, Tervaert JW, Van Der Meer J, van Son WJ, and The ...
EBV Thymidine Kinase, 0.1 mg. Thymidine kinase (TK) belongs to a group of enzymes such as dihydrofolate reductase, thymidylate synthase, and DNA polymerase that are involved in DNA synthesis and precursor production.
Valaciclovir belongs to a family of molecules. Valaciclovir is a prodrug, an esterified version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir (10-20%). It is converted by esterases to the active drug aciclovir, as well as the amino acid valine, via hepatic first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase.[citation needed] Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of ...
Although acyclovir (ACV) is an effective antiviral agent, herpes simplex virus (HSV) that is resistant to treatment can be a serious clinical problem in immunocompromised patients. It has been estimated that ACV-resistant (ACVr) HSV appears in as many as 5% of this population upon treatment (4, 10). Clinically significant drug resistance implies evasion of drug action but retention of pathogenesis. The vast majority of mutations associated with clinical drug resistance occur in the viral thymidine kinase (TK) gene (tk), which encodes the enzyme that selectively activates ACV. The phenotypes of clinical isolates with mutant TKs typically fall into one of three categories: altered substrate specificity, low TK activity (TKL), or lack of measurable TK activity (TK−) (11, 12, 26). That viruses lacking TK activity are pathogenic has been puzzling. Although TK is not required for growth in cell culture, it is essential for pathogenesis in mouse models of HSV infection, in particular, for ...
The human growth hormone (hGH) transient assay system described here is based on the expression of hGH directed by cells transfected with hGH fusion genes. Levels of secreted hGH in the medium, measured by a simple radioimmunoassay, are proportional to both levels of cytoplasmic hGH mRNA and the amount of transfected DNA. The system is extremely sensitive, easy to perform, and is qualitatively different from other transient expression systems in that the medium is assayed and the cells themselves are not destroyed. The hGH transient assay system is appropriate for analyses of regulation of gene expression and was utilized here to investigate the effect of the simian virus 40 enhancer on the herpes simplex virus thymidine kinase promoter and the effect of zinc on the mouse metallothionein-I promoter. The expression of hGH can also be used as an internal control to monitor transfection efficiency along with any other transient expression system. All cell types tested thus far (including AtT-20, ...
Most individuals have no or only minimal signs or symptoms from HSV-1 or HSV-2 infection. ELLANSÉ™ with its four distinctive versions, lasting from 12 months up to 4 years, allow you to choose how long you would like the results to last, eliminating the need for frequent repeat treatments. Herpes infections are common among women of reproductive age (i.e., aged 15-44 years). Patients older than 65 years are usually considered ineligible for ASCT. In U. The sympathetic fibres parallel the parasympathetic fibres as they supply the same areas. Herpes simplex virus thymidine kinase (HSV-TK) is widely used in gene therapy.. TheBody. First, a lot of time and energy worrying that your partner will get herpes. The culprit responsible for cold sores is the herpes simplex virus. IgM antibodies are produced immediately after infection. What electrodesiccation uses in destroying chlamydia is an electric current. Make research projects and school reports about Canker Sores easy with credible articles ...
Multiple labs have reported that mammalian ovaries contain oogonial stem cells (OSCs), which can differentiate into oocytes that fertilize to produce offspring. However, the physiological relevance of these observations to adult ovarian function is unknown. Here we performed targeted and reversible ablation of premeiotic germ cells undergoing differentiation into oocytes in transgenic mice expressing the suicide gene, herpes simplex virus thymidine kinase (HSVtk), driven by the promoter of stimulated by retinoic acid gene 8 (Stra8), a germ cell-specific gene activated during meiotic commitment. Over a 21-day ablation phase induced by the HSVtk pro-drug, ganciclovir (GCV), oocyte numbers declined due to a disruption of new oocyte input. However, germ cell differentiation resumed after ceasing the ablation protocol, enabling complete regeneration of the oocyte pool. We next employed inducible lineage tracing to fate map, through Cre recombinase-mediated fluorescent reporter gene activation only in Stra8
It is called suicide gene therapy. And this is the concept: find a gene coding for an enzyme that human cells dont have. Insert that gene only into cancer cells--not normal cells. This enzyme works by taking a harmless pro-drug and converting it into a toxic compound. Early attempts at this therapy used the enzyme thymidine kinase from the herpes simplex virus. This enzyme converts the drug ganciclovir into a compound that stops DNA synthesis. If a cancer cell cant make new DNA, it will eventually die ...
Figure and Images: Expression of functional MMP-9 by GLV-1h255-infected tumor cells. (A) Expression cassettes of GLV-1h68 and GLV-1h255. In GLV-1h255 the insert in the Tk locus was replaced by the human mmp-9 gene under control of the PSE promoter. PSEL, synthetic early/late promoter; PSE, synthetic early promoter; P7.5, VACV p7.5 K early/late promoter; P11, VACV p11 late promoter; Tk, thymidine kinase locus, Ha, hemagglutinin locus. (B) Expression of virus-encoded MMP-9 (92 kDa) in GLV-1h255 infected PC-3 cells and supernatants in vitro, β-actin (42 kDa) was used as a loading control. (C) Activity of the MMP-9 protein was tested by gelatin zymography. Lysates and supernatants of infected A549 cells were isolated and separated by non-reducing SDS-PAGE. In zymography, cleavage of the substrate by MMP-9 resulted in a clear band. ...
BioAssay record AID 221799 submitted by ChEMBL: Compound was tested for antitumor activity against thymidine kinase deficient human B-lymphoblast Raji/0 cells.
The test item triethoxy(3-thiocyanatopropyl)silane was assessed for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The selection of the concentrations used in the main experiment was based on data from the pre-experiment. In the main experiment 1.3 mM (with metabolic activation) and 1 mM (without metabolic activation) were selected as the highest concentrations. The experiment with and without metabolic activation was performed as a 4 h short-term exposure assay. Based on the solubility test DMSO was used as solvent (final concentration 1% DMSO v/v). The test item was investigated at the following concentrations: with metabolic activation: 0.05, 0.1, 0.2, 0.5, 0.7, 0.9, 1.1 and 1.3 mM and without metabolic activation: 0.005, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5 and 1 mM Precipitation of the test item was noted in the pre-experiment at a concentration of 2.5 mM. Growth inhibition was observed in the main experiment with and without metabolic ...
Acquistare indescribably forzest 20 buy online gli integratori che elencheremo in questo report è al 100% legale per la Legge Italiana. In another embodiment, a fusion protein comprised of a modified form of the tet repressor (TetR) and a transactivation domain or a domain (eg, a dimerization domain) which recruits a transcriptional activator (eg, an endogenous transcriptional activator) to interact with the fusion protein by a protein-protein interaction (eg, a non-covalent interaction) is introduced into a cell. Coli is also found in this environment ( 60, 61). Viral resistance to acyclovir may occur due to loss of thymidine kinase activity, levitra malaysia alterations in thymidine kinase substrate specificity, or decreased DNA-polymerase sensitivity. I have heard excellent things about blogenginenet! Im not very internet smart so Im not 100% certain? «Lady Gaga dedicates her new Little Monsters tattoo to her fans». The decision making it is only has not a new buy retin a cream ...
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The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. This creates dTMP and is the first step in the biosynthesis of dTTP, which is one component required for DNA replication. The encoded protein, whose levels fluctuate depending on the cell cycle stage, can act as a low activity dimer or a high activity tetramer. High levels of this protein have been used as a biomarker for diagnosing and categorizing many types of cancers. [provided by RefSeq, Oct 2016 ...
1E2P: The Effect of Substrate Binding on the Conformation and Structural Stability of Herpes Simplex Virus Type 1 Thymidine Kinase
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FLT was developed to provide a measure of tumor proliferation because it is taken up by cells and retained after phosphorylation by thymidine kinase 1. Thymidine kinase 1 increases as cells enter the DNA synthetic phase, and previous work has shown that FLT retention generally correlates with other measures of tumor proliferation. The most likely use of FLT will be in monitoring treatment response, but such studies need to consider the different methods for measuring FLT retention in tumors and their reproducibility.. The most common method of measuring tracer retention has been through the use of the semiquantitative approach of the SUV. The SUV uses the measurement of activity within a ROI along with the injected dose and the weight of the patient to calculate the desired variable. To take into account differences in the proportion of fat in patients, some investigators have adjusted the SUV by using lean body mass, ideal body weight, or even body surface area. When studying the ...
gbr:Gbro_2907 K00857 thymidine kinase [EC:2.7.1.21] , (GenBank) Thymidine kinase (A) MSASAELVFYYGPMGAGKSTLALQTHFNQRQQGRSGVLLTKDDRSNRPLVTSRIGLAAEA IAVDDHTDVHALITGRGIPDFLVCDEAQFLTIAQVDQLAGLVDDHAVSVFAYGLLTDFRS VLFPGSARLVEIADEIHRMQAVVLCWCGRDACLNARIVNGRMVHAGELIAIGDTGDGPVH YRPLCRRHFTQGRIDAGGEPGPVDTNSQNPFSTG ...
srp:SSUST1_0992 K00857 thymidine kinase [EC:2.7.1.21] , (GenBank) tdk; thymidine kinase (A) MAQLYYKYGTMNSGKTIEILKVAHNYEEQGKPVVIMTSALDTRDAFGVVSSRIGMRRDAV AIDDDMDIFGFIEKMEPRPYCVLIDEAQFLRRHHVYALARVVDELDVPVMAFGLKNDFRN ELFEGSQHLLLLADKLDEIKTICQYCSKKATMVLRTQDGKPTYEGEQIQIGGNETYIPVC RKHYFSPEIKELP ...
Generation of MT-III-deficient mice. The mouse MT-III gene was isolated from a 129Sv genomic library (Palmiter et al., 1992). A disruption vector was constructed by replacing a 2.2 kbXhoI-NdeI region containing the promoter and exons 1 and 2 with a neomycin resistance cassette and inserting thymidine kinase genes at BamHI and BstEII sites in the 5′ and 3′ flanking regions, respectively. Electroporation and selection of AB1 embryonic stem cells was performed as described (Thomas et al., 1995). Colonies were screened for targeting by PCR and confirmed by Southern blot analysis of DNA digested withSstI by using a 0.6 kb BstEII-NdeI fragment as a probe. Eight positive clones were identified from 840 clones screened. Four clones were used to generate chimeric mice as described (Thomas et al., 1995), but only one clone transmitted through the germline, and it was used to establish a line of mice carrying the disrupted allele. F2 and F3 generation C57Bl/129Sv hybrid mice of both sexes were used in ...
Rabbit polyclonal antibody raised against synthetic peptide of TK1. A synthetic peptide corresponding to N-terminus of human TK1. (PAB5614) - Products - Abnova
TY - CHAP. T1 - Osteonectin promoter-mediated suicide gene therapy of prostate cancer. AU - Hsiao, Wan Chi. AU - Sung, Shian Ying. AU - Chung, Leland W.K.. AU - Hsieh, Chia Ling. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Suicide gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene, combined with the prodrug ganciclovir (GCV) medication, is a promising approach for the treatment of malignant tumors, including prostate cancer. The success of this therapeutic strategy requires tissue- or tumor-specific gene expression and efficient gene delivery. In this chapter, we describe the experimental protocols of key methodologies, including promoter construction, reporter assay, adenoviral vector construction and preparation, HSV-tk enzymatic assay and cytotoxicity assay to evaluate the specificity and efficacy of osteonectin promoter-mediated HSV-tk/GCV suicide gene therapy of prostate cancer.. AB - Suicide gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene, combined ...
TY - JOUR. T1 - Construction of a differentiated human hepatocyte cell line expressing the herpes simplex virus-thymidine kinase gene. AU - Kobayashi, Naoya. AU - Miyazaki, Masahiro. AU - Westerman, Karen A.. AU - Noguchi, Hirofumi. AU - Sakaguchi, Masakiyo. AU - Totsugawa, Toshinori. AU - Watanabe, Takamasa. AU - Matsumura, Toshihisa. AU - Fujiwara, Toshiyoshi. AU - Leboulch, Philippe. AU - Tanaka, Noriaki. AU - Namba, Masayoshi. PY - 2001. Y1 - 2001. N2 - Transient support using a hybrid artificial liver (HAL) device is a promising treatment for the patients with acute liver failure. Primary human hepatocytes are an ideal source for HAL therapy; however, the number of human livers available for hepatocyte isolation is limited by competition for use in whole organ transplantation. To overcome this problem, we previously established a highly differentiated human fetal hepatocyte cell line OUMS-29. Considering the potential risk when using these genetically engineered cells in humans, additional ...
TY - JOUR. T1 - Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter. AU - Ahn, M.. AU - Lee, S. J.. AU - Li, Xiaochun. AU - Jiménez, J. A.. AU - Zhang, Y. P.. AU - Bae, K. H.. AU - Mohammadi, Y.. AU - Kao, Chinghai. AU - Gardner, Thomas. PY - 2009/1. Y1 - 2009/1. N2 - Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the ...
We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining CCl4 (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type (WT) and Tg mice, GCV induced cell death in ∼50% of HSCs from Tg, but not WT, mice. In TG mice treated with CCl4+AA+GCV, there was a significant decrease in GFAP and desmin-positive cells, compared to WT mice (∼65% reduction; ...
Acyclovir is a potent and selective antiviral agent. Unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (HSV-1) orofacial infections. We have developed a laboratory acyclovir-resistant HSV-1 mutant. The natural course of acyclovir-resistant HSV-1 keratitis was found to be less virulent than that observed in wild type HSV-1 keratitis, but the rate of ganglionic latency was as high as that induced by the parental strain. In vitro studies and in vivo observation of rabbit corneas infected with acyclovir-resistant HSV-1 both demonstrated a significant sensitivity to vidarabine and bromovinyldeoxyuridine ([E]-5-[2-bromovinyl]-2-deoxyuridine). The thymidine kinase activity of the acyclovir-resistant mutant was 69% of that of the wild type HSV-1 ...
The herpesvirus family comprises several widespread infectious pathogens. They infect a variety of animal hosts, including humans and cause complex clinical outcomes. Recently, the possible correlation between genital infection by human herpesviruses (HHVs) and male infertility has attracted considerable attention. In this chaper, we investigated the mechanism of HHV‐1‐induced infertility in transgenic (Tg) rats and its possible correlation with infertility in human males. Ectopic expression of HHV‐1 thymidine kinase (TK) in the testis of Tg rats increased male infertility. In addition, truncated TK proteins were found in postmeiotic spermatids of Tg rat testis, leading to progressive degeneration of germ cells and vacuolization of the seminiferous epithelium. These findings suggest the possibility that a similar process occurs within HHV‐infected human germ cells.
TY - JOUR. T1 - Ablation of Neurogenesis Attenuates Recovery of Motor Function after Focal Cerebral Ischemia in Middle-Aged Mice. AU - Sun, Fen. AU - Wang, Xiaomei. AU - Mao, Xiao Ou. AU - Xie, Lin. AU - Jin, Kunlin. PY - 2012/10/26. Y1 - 2012/10/26. N2 - Depletion of neurogenesis worsens functional outcome in young-adult mice after focal cerebral ischemia, but whether a similar effect occurs in older mice is unknown. Using middle-aged (12-month-old) transgenic (DCX-TK(+)) mice that express herpes simplex virus thymidine kinase (HSV-TK) under control of the doublecortin (DCX) promoter, we conditionally depleted DCX-positive cells in the subventricular zone (SVZ) and hippocampus by treatment with ganciclovir (GCV) for 14 days. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery (MCAO) or occlusion of the distal segment of middle cerebral artery (dMCAO) on day 14 of vehicle or GCV treatment and mice were killed 24 hr or 12 weeks later. Increased infarct volume ...
Objective: Neural stem cells (NSC) have an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive gliomas. Here, we demonstrate that the non-invasive intranasal administration of tumor-targeting NSC is able to deliver a novel suicide gene (TK007) to intracerebrally growing human glioblastoma xenografts.. Method: Murine NSC were genetically modified to express the novel herpes simplex virus thymidine kinase variant (TK007). The biological activity of the NSC-mediated TK007/ganciclovir (GCV) system was assessed in cell survival and bystander assays using various human glioma cell lines. Therapeutic effects of intratumoral (3x105 cells) and intranasal (1.5x106) NSC-TK007 application alone and the sequential combination of both was tested using an intracranial U87 human glioblastoma model in nude mice. All animals received 50 mg/kg GCV i.p. for five consecutive days. Two control groups received either NaCl instead of GCV or NSC containing the empty ...
Preferred Name: Valacyclovir Definition: The hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir. Orally administered, valacyclovir is rapidly converted to acyclovir which inhibits viral DNA replication after further conversion to the nucleotide analog acyclovir triphosphate by viral thymidine kinase, cellular guanyl cyclase, and a number of other cellular enzymes. Acyclovir triphosphate competitively inhibits viral DNA polymerase; incorporates into and terminates the growing viral DNA chain; and inactivates viral DNA polymerase. The greater antiviral activity of acyclovir against herpes simplex virus (HSV) compared with varicella-zoster virus (VZV) is due to its more efficient phosphorylation by HSV thymidine kinase. NCI-GLOSS Definition: A substance that is being studied in the prevention of fungal, bacterial, and viral infections in patients undergoing donor stem cell transplantation with cells that are infected with cytomegalovirus. It belongs to the family of drugs ...
Glioblastoma is a highly aggressive malignant tumor involving glial cells in the human brain. We used high-throughput sequencing to comprehensively profile the small RNAs expressed in glioblastoma and non-tumor brain tissues. MicroRNAs (miRNAs) made up the large majority of small RNAs, and we identified over 400 different cellular pre-miRNAs. No known viral miRNAs were detected in any of the samples analyzed. Cluster analysis revealed several miRNAs that were significantly down-regulated in glioblastomas, including miR-128, miR-124, miR-7, miR-139, miR-95, and miR-873. Post-transcriptional editing was observed for several miRNAs, including the miR-376 family, miR-411, miR-381, and miR-379. Using the deep sequencing information, we designed a lentiviral vector expressing a cell suicide gene, the herpes simplex virus thymidine kinase (HSV-TK) gene, under the regulation of a miRNA, miR-128, that was found to be enriched in non-tumor brain tissue yet down-regulated in glioblastomas, Glioblastoma cells
Thymidine kinase (TK) belongs to the group of oncofetal enzymes. It catalyzes thymidine transformation to thymidine monophosphate in the presence of ATP. Elevated serum levels of TK can be found above all in the acute stages of malignant diseases of the hematopoietic system, in the bronchoendogenic carcinoma, carcinoma of the prostate, testis, and bladder.. ...
ID PCP1 preliminary; circular DNA; SYN; 3600 BP. XX AC S62800; ATCC37351; XX DT 01-JUL-1993 (Rel. 7, Created) DT 01-JUL-1995 (Rel. 12, Last updated, Version 1) XX DE Vertebrate/E.coli plasmid vector pCP1 - incomplete. XX KW cloning vector. XX OS Cloning vector OC Artificial sequences; Cloning vehicles. XX RN [1] RC plasmid from pUC9 & vaccinia virus 7.5kDa gene RC pCP1 from pCAT & plasmid RC pMM24 from pMM23 & SV40 72-bp repeats RA Cochran M.A., Mackett M., Moss B.; RT Eukaryotic transient expression system dependent on transcription RT factors and regulatory DNA sequences of vaccinia virus; RL Proc. Natl. Acad. Sci. U.S.A. 82:19-23(1985). XX RN [2] RC plasmid from pBR328 RC pGS8 from plasmid & vaccinia virus TK gene RC pMM1 from pUC9 & vaccinia virus TK gene RC pMM2 from pUC9 & vaccinia virus TK gene RC pMM3 from pMM1 & pMM2 RC pMM4 from pMM3 RC pMM5 from pMM4 RC pGS15 from pUC9 & pAG4 RC pGS19 from pGS15 & linker RC pGS20, pGS21 from pGS19 & pGS8 RC [pGS30 from cat gene] RC pCAT from pBR328 ...
The bystander effect refers to the death of unmodified tumor cells when in contact with ganciclovir (GCV)-exposed, herpes simplex virus-thymidine kinase (HSV-TK)-modified tumor cells. Although the exact mechanism or mechanisms involved in mediating the bystander effect in vivo are unknown, our fin …
Reliable markers for monitoring bladder tumor therapy are needed to evaluate treatment effectiveness. Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and therefore proliferation-dependent. Serum concentration of TK1 (STK1) correlates with malignancy in various types of cancer, thus reflecting treatment results. This study explores for the first time the use of STK1 concentration, both as a prognostic marker and to monitor the outcome of bladder carcinoma surgery. STK1 in 56 bladder carcinoma patients was measured pre-operatively, and post-operatively at 1 week and 1, 3, and 6 months, using an immune ECL dot blot assay. An anti-TK1 chicken IgY antibody was used to determine STK1 concentrations. Mean pre-operative STK1 of bladder carcinoma patients was significantly higher than that of healthy individuals, with no overlap of individual values. STK1 concentrations increased significantly with tumor stage (I-III) and T-values (T1-T2), but not tumor grade (G1-G4). STK1 gradually ...
In the stab-injured spinal cord of GFAP-TK mice not given GCV, we found that all TK-expressing cells also expressed GFAP, and that ,98%, but not all, of GFAP-expressing reactive astrocytes also expressed detectable levels of transgene-derived TK (Fig. 2A-D,G). The inability to detect TK in all GFAP-expressing cells may be attributable to the discontinuous activity of the GFAP gene and differences in the intracellular half-life of the GFAP and TK proteins, as discussed elsewhere (Bush et al., 1999; Imura et al., 2003). We found no evidence for TK expression by cells that did not express GFAP.. To evaluate the degree of astrocyte cell division induced by SCI, we administered BrdU during the first 4 d after injury (Fig. 1A). At 14 d after injury, control mice exhibited many BrdU-labeled cells in tissue immediately adjacent to the stab wound (Fig. 2E,F); most of these BrdU-labeled cells expressed GFAP (Fig. 2H) and TK.. There was no qualitatively detectable difference in the response to SCI in all ...
AVIRAX Fabrigen Acyclovir Antiviral Action And Clinical Pharmacology: Acyclovir, a synthetic acyclic nucleoside analog, is a substrate with a high degree of specificity for herpes simplex and varicella-zoster specified thymidine kinase. Acyclovir is a poor substrate for host cell-specified thymidine kinase. Herpes simplex and varicella-zoster specified thymidine kinase transform acyclovir to its monophosphate which is then transformed by a number of cellular enzymes to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate is both an inhibitor of, and a substrate for, herpesvirus-specified DNA polymerase. Although the cellular a-DNA polymerase in infected cells may also be inhibited by acyclovir triphosphate, this occurs only at concentrations of acyclovir triphosphate which are higher than those which inhibit the herpesvirus-specified DNA polymerase. Acyclovir is selectively converted to its active form in herpesvirus-infected cells and is thus preferentially taken up by these ...
The nucleotide sequence of the UL31 open reading frame is predicted to encode a basic protein with a hydrophilic amino terminus and a nuclear localization signal. To identify its gene product, we constructed a viral genome in which the thymidine kinase gene was inserted between the UL31 and UL32 open reading frames. The thymidine kinase gene was then deleted, and in the process, the 5 terminus of the UL31 open reading frame was replaced with a 64-bp sequence in frame with the complete, authentic sequence of the UL31 open reading frame. The inserted sequence encoded a hydrophilic epitope derived from glycoprotein B of human cytomegalovirus and for which a monoclonal antibody is available. We report that in infected cells, the tagged protein localized in and was dispersed throughout the nucleus. Nuclear fractionation studies revealed that the UL31 protein partitions with the nuclear matrix. The protein is phosphorylated in infected cells maintained in medium containing 32Pi. ...
The test substance was tested in an Ames test at concentrations up to the precipitation level (5000 ug/plate). In a plate incorporation and a pre-incubation assay (both performed in triplicate), the test substance did not induce mutations (base-pair substitution and frame-shift type) in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, as well as in E. coli WP2 uvr A both in presence and absence of metabolic activation (Harlan 2013j). The analogue is considered to be non mutagenic in the mouse lymphoma thymidine kinase locus using the cell line L5178Y (BSL2010e) and no chromosomal changes were observed in a chromosome aberration test in Chinese hamster lung fibroblasts (V79) (BSL 2010d). Both tests were performed in presence and absence of metabolic activation. Based on the similar outcome in the Ames test and the similarities between the test substance and the analogue, it is concluded that it is not expected that the test substance will induce mutagenic or clastogenic effects. No ...
A valid GLP study was performed to investigate the potential of the test item to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The method followed was that described in OECD TG 476. The assay was performed in three independent experiments, using two parallel cultures each. Experiment I, and II were performed with and without liver microsomal activation and a treatment period of 4 hours. The supplementary experiment III was solely performed with metabolic activation (4 hours treatment) to cover the cytotoxic range of approximately 10- 20% RTG that was not covered in the second experiment with metabolic activation. The concentration range of the main experiments was limited by the solubility of the test item in aqueous media and by cytotoxic effects. Relevant cytotoxic effects occurred at 40 µg/mL in the first experiment without metabolic activation and at 80.0 µg/mL in the presence of metabolic activation. In the second experiment cytotoxicity was ...
DiviTum™ assay determines the enzymatic activity of TK in patient samples. During the assay procedure, thymidine is replaced by its synthetic analog bromodeoxyuridine (BrdU), which gets phosphorylated and then incorporated into a synthetic DNA strand fixated in each well of a 96-well ELISA immunosorbent titer-plate.. The extent of BrdU incorporation depends on the activity of TK present in the serum sample; the more TK activity in the sample, the more BrdU is incorporated into synthetic DNA strands in the titer-plate well. The synthetic BrdU is then detected with anti-BrdU specific antibodies using the well-known ELISA assay technique. The DiviTum™ technology amplifies the signal, enabling the assay to measure thymidine kinase activity with high sensitivity.. ...
G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate the safety of stereotactic intratumoral administration when given 24 hours prior to a single 5 Gy radiation dose in patients with recurrent m …
An enzyme (abbreviated tk) which plays an important role in the making of thymidine triphosphate from thymine -- the only way thymine, cytosine, and oth...
Acyclovir, famciclovir, and ganciclovir are guanosine analogs that are used as viral DNA polymerase inhibitors to treat HSV, VZV, and EBV. The three analogs require phosphorylation for activation. The first step in phosphorylation is monophosphorylation by the HSV/VZV thymidine kinase; further phosphorylation is then performed by the host cells to form the triphosphate. Finally, the drug is incorporated into the viral DNA molecule, terminating replication. Resistance arises when the virus lacks thymidine kinase and these analogs cannot be activated; therefore, cidofovir, which does not require phosphorylation by a viral kinase, must be used ...
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The GMO is a viral suspension of the recombinant virus JX-594. JX-594 is a non-integrative, replicative, propagative, recombinant VV derived from the commonly used commercial vaccine Wyeth strain. JX-594 differs by three genetic modifications from the wild type Wyeth strain: 1) disruption of the viral thymidine kinase (TK) gene by, 2) insertion of the human granulocyte macrophage-colony stimulating factor (hGM-CSF) gene and 3) insertion of the lacZ gene. ...
EBV and KSHV are associated with a variety of malignancies including some lymphomas, carcinomas and other malignancies. We anticipate that viral TK expression will differ among tumor types and will be adjusted with standard chemotherapies and some investigational agents. This exploratory study is aimed in part at evaluating whether standard regimens or investigational regimens might bring about sufficient activation of the EBV-TK or KSHV-TK in tumors to be therapeutically useful if used in conjunction with FIAU as a radiopharmaceutical ...
EBV and KSHV are associated with a variety of malignancies including some lymphomas, carcinomas and other malignancies. We anticipate that viral TK expression will differ among tumor types and will be adjusted with standard chemotherapies and some investigational agents. This exploratory study is aimed in part at evaluating whether standard regimens or investigational regimens might bring about sufficient activation of the EBV-TK or KSHV-TK in tumors to be therapeutically useful if used in conjunction with FIAU as a radiopharmaceutical ...
Beta-catenin/Tcf reporter mice. These mice express GFP gene under the control of the Tcf/Lef binding sites and a minimal thymidine kinase promoter from the TOPFLASH plasmid. Immunohistochemistry with a GFP antibody can be used to assess the Tg expression in the intestine. In other organs except for the intestine. In the splenocytes, expression of GFP was observed by FACS analysis, In other organs, the GFP expression patterns are not examined yet ...
SWISS-MODEL Template Library (SMTL) entry for 1qhi.1. HERPES SIMPLEX VIRUS TYPE-I THYMIDINE KINASE COMPLEXED WITH A NOVEL NON-SUBSTRATE INHIBITOR, 9-(4-HYDROXYBUTYL)-N2-PHENYLGUANINE
In anticipation of a phase I clinical trial in GBM patients using an immunotherapeutic approach that combines Ad-Flt3L with Ad-TK+GCV, it was critical to determine the optimal cytotoxic agent to use in this approach. Therefore, we compared the efficacy and neurotoxicity of Ad-TK+GCV with Ad vectors encoding the proapoptotic cytokines TNF-α, TRAIL, and FasL. Our hypothesis was that Ad-TK+GCV would exhibit superior efficacy and safety when compared with Ads expressing proapoptotic cytokines. Because Ad-TK kills proliferating cells in the presence of GCV (37), we expected this agent to have a powerful antitumor effect due to the presence of mitotic tumor cells within GBM. Also, the bystander effect of phosphorylated GCV would amplify the cytotoxic effect of this approach (37). The highest therapeutic efficacy was indeed achieved when using Ad-TK+GCV by itself for small tumors, and in combination with Ad-Flt3L for large tumors. Although all the proapoptotic Ads certainly induced apoptosis in vitro ...
Studying the biochemical determinants of FUra efficacy is still a major concern of todays chemotherapy (19, 20). Among the numerous factors likely to improve cell sensitivity, the role of tumoral enzymes involved in the conversion of prodrug FUra into active metabolites has been studied extensively. Because tumor response to fluoropyrimidines is multifactorial, determining a single marker of FUra efficiency remains hazardous and is often prone to controversy, even in vitro. For example, the activity of TK has been presented as a key determinant of response to FUra (21-23), whereas other studies have correlated high TK activity with resistance to fluoropyrimidine (24, 25), a fact that we experienced as well after transfecting the viral HSV1-TK gene into HT29 cells.4 Similarly, although UP has been described as an important enzyme responsible for FUra anabolism in several models (26), an attempt to modulate drug response after human UP transfection into MCF7 cells in our laboratory failed to ...
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The MTKP 97-12 cell line was produced by transfecting LMTK- cells with the expression plasmid pMTp97b that contains a cDNA sequence coding for the p97 melanoma associated antigen.
"Thymidine kinase". Medical Dictionary. Merriam-Webster. Retrieved 5 April 2013. Gentry GA (1992). "Viral thymidine kinases and ... encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine ... The enzymes thymidine kinase and ribonucleotide reductase in cells are responsible for DNA synthesis and are only expressed in ... kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis. The tumour ...
replacement of thymidine kinase (TK)). RCN was successful in 50% of voluntary participants allowing them to survive subsequent ...
Gentry GA (1992). "Viral thymidine kinases and their relatives". Pharmacology & Therapeutics. 54 (3): 319-55. doi:10.1016/0163- ...
Thymidine can be phosphorylated by thymidine kinase (TK). Uridine can be phosphorylated by uridine kinase (UK). Cytidine can be ... Deoxycytidine can be phosphorylated by deoxycytidine kinase (DCK). Adenosine uses the enzyme adenosine kinase, which is a very ...
"Induction of endogenous virus and of thymidine kinase by bromodeoxyuridine in cell cultures transformed by Friend virus". ... "Identification and Characterization of Mitochondrial Factors Modulating Thymidine Kinase 2 Activity". Nucleosides, Nucleotides ... Induction of Endogenous Virus and of Thymidline Kinase. "Archived copy" (PDF). Archived (PDF) from the original on September 24 ... AZT is a thymidine analogue. AZT works by selectively inhibiting HIV's reverse transcriptase, the enzyme that the virus uses to ...
... the first betaherpesvirus with a thymidine kinase gene". Journal of General Virology. 87 (Pt 10): 2781-2789. doi:10.1099/vir. ...
... thymidine kinase, thymidylate synthetase, DNA polymerase and many others. While no other human tumor virus possesses these same ... ORF45 - tegument protein, interacts with p90 ribosomal S6 kinases (RSKs) to modulate the ERK/RSK MAPK signaling pathway ... ORF36 - vPK - viral protein kinase with multiple roles in replication cycle ORF37 - SOX - dual function protein - DNase ... "The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus". Nature Medicine ...
Pellicer, A; Wigler, M; Axel, R; Silverstein, S (1978). "The transfer and stable integration of the HSV thymidine kinase gene ... "Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells". Cell. 11 (1): 223-32. doi:10.1016/0092-8674( ...
In gene-deleted vaccines, the thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in ...
Hamel, W; Magnelli, L; Chiarugi, VP; Israel, MA (June 1996). "Herpes simplex virus thymidine kinase/ganciclovir-mediated ... "Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins". Proceedings of the ... of the herpes simplex virus thymidine kinase/ganciclovir system in vitro". Gene Ther. 3 (1): 85-92. PMID 8929915. Mesnil, Marc ...
An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection. A distinction can be made ...
An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection.[citation needed] Positive and ...
Griffiths A (December 2011). "Slipping and sliding: frameshift mutations in herpes simplex virus thymidine kinase and drug- ...
Viral proteins like viral thymidine kinase can be used for specific targeting of a drug. By introducing a prodrug only ... Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells. GSK3 is involved in promoter activation ... kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells". Journal of Immunology. 174 (9): ...
FLT accumulates in proliferating cells where it indicates the activity of the enzyme thymidine kinase. Cell division can be ... FLT is phosphorylated as though it were thymidine, and is subsequently incorporated into DNA. Thymidine is essential for DNA ...
In this case the study uses the transfer of the Herpes simplex virus type I thymidine kinase (HSVtk) as the cytotoxic gene. ... "Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins". Proceedings of the ...
Deletion of thymidine kinase (TK) from the JX-594 genome prevents virus replication in normal cells. The immunostimulatory ... encoding thymidine kinase or TK) in the J segment of the Wyeth strain vaccinia virus. Elimination of TK from the JX-594 genome ...
Brinster R, Chen HY, Trumbauer M, Senear AW, Warren R, Palmiter RD (1981). "Somatic expression of herpes thymidine kinase in ...
"Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829-34. doi:10.1042/0264-6021:3560829. PMC ... cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine kinase activity. • ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ...
However, most of the mutations occur in the thymidine kinase gene rather than the DNA polymerase gene. Another analysis has ... In clinical setting, the mutations in either the thymidine kinase gene or DNA polymerase gene has caused resistance to ...
... interaction with E2F and regulation of the murine thymidine kinase promoter". J. Mol. Biol. 293 (5): 1005-15. doi:10.1006/jmbi. ...
... studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage. ... BI811283 is a small molecule inhibitor of the aurora B kinase protein being developed by Boehringer Ingelheim for use as an ... Sutendra G, Michelakis ED (2013). "Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology". Frontiers in ... a novel inhibitor of Aurora B kinase, on tumor senescence and apoptosis". J. Clin. Oncol. 28 (15 Suppl e13632): e13632. doi: ...
... interaction with E2F and regulation of the murine thymidine kinase promoter". Journal of Molecular Biology. 293 (5): 1005-15. ... interaction with E2F and regulation of the murine thymidine kinase promoter". Journal of Molecular Biology. 293 (5): 1005-15. ...
Replication and expression of thymidine kinase and human globin genes microinjected into mouse fibroblasts. Proc. Natl. Acad. ...
First, cellular thymidine kinases phosphorylate the parent form significantly less rapidly than does the viral thymidine kinase ... Within a virally infected cell a viral thymidine kinase adds a phosphate group to the penciclovir molecule; this is the rate- ... Cellular (human) kinases then add two more phosphate groups, producing the active penciclovir triphosphate. This activated form ...
Aciclovir acts as a nucleoside analog which specifically target herpes virus-infected cells using viral thymidine kinase (TK). ... Reactivation in HSV requires the stress response enzyme c-Jun N-terminal kinase (JNK), which is responsive to stressors such as ... which is subsequently phosphorylated to active aciclovir triphoshate by cellular kinases, thus selectively inhibiting viral DNA ...
... researchers were able to insert a herpes simplex virus thymidine kinase coding gene into tumor cells. This "suicide gene" is ...
AAV-2-HSV-TK: Herpes simplex virus type 1 thymidine kinase (HSV-TK) is a common anti-cancer therapy that converts the ... "Persistent anti-tumor effects via recombinant adeno-associated virus encoding herpes thymidine kinase gene monitored by PET- ... 2015). "Combined antitumor gene therapy with herpes simplex virus thymidine kinase and short hairpin RNA specific for mammalian ...
Interaction of human thymidine kinase 1 with p21(Waf1). „Biochem. J.". 356 (Pt 3), s. 829-34, 2001. PMID: 11389691. ... Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ...
Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. ... Norbury C (1995). "Cdk2 protein kinase (vertebrates)". In Hardie DG, Hanks S (eds.). Protein kinase factsBook. Boston: Academic ... Additionally, CDK4/6 and CDK2 are also inactive because CDK4/6 are bound by INK4 family members (e.g., p16), limiting kinase ... Two families of genes, the cip/kip (CDK interacting protein/Kinase inhibitory protein) family and the INK4a/ARF (Inhibitor of ...
OST is a component of the translocon in the endoplasmic reticulum (ER) membrane. A lipid-linked core-oligosaccharide is assembled at the membrane of the endoplasmic reticulum and transferred to selected asparagine residues of nascent polypeptide chains by the oligosaccharyl transferase complex.[3] The active site of OST is located about 4 nm from the lumenal face of the ER membrane.[4] It usually acts during translation as the nascent protein is entering the ER, but this cotranslational glycosylation is nevertheless called a posttranslational modification. A few examples have been found of OST activity after translation is complete.[5][6] Current opinion is that post-translational activity may occur if the protein is poorly folded or folds slowly.[6] ...
cAMP binds to and releases an active form of protein kinase A (PKA). Next, PKA phosphorylates phosphorylase kinase, which, in ... Glycogen phosphorylase kinase activates glycogen phosphorylase in the same manner mentioned previously. ... The increased calcium availability binds to the calmodulin subunit and activates glycogen phosphorylase kinase. ...
... the Herpes simplex virus thymidine kinase (HSV TK). ...
A protein kinase drifting around on the outer chloroplast membrane can use ATP to add a phosphate group to the Toc34 protein, ... Stocking, C. R. & Gifford, E. M. (1959). "Incorporation of thymidine into chloroplasts of Spirogyra". Biochemical and ... It can be regulated through phosphorylation, but by a different protein kinase than the one that phosphorylates Toc34.[45] Its ...
3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". ... 1-phosphatidylinositol-3-kinase activity. • phosphatidylinositol-4,5-bisphosphate 3-kinase activity. • kinase activity. • ... protein kinase activator activity. • 1-phosphatidylinositol-4-phosphate 3-kinase activity. • protein serine/threonine kinase ... phosphatidylinositol 3-kinase complex. • cytosol. • phosphatidylinositol 3-kinase complex, class IA. • plasma membrane. • ...
Phosphoinositide 3-kinase. References[edit]. *Stein RC( 2001) Prospects for phosphoinositide 3-kinase inhibition as a cancer ... Class II PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain ... Class II PI 3-kinases were the most recently identified class of PI 3-kinases and little is currently known about these enzymes ... Foster FM, Traer CJ, Abraham SM, and Fry MJ (2003) The phosphoinositide (PI) 3-kinase family J Cell Sci 116:3037-3040.[2] ...
Kinase. L[cuir in eagar , athraigh foinse]. For substances with an l- or L- prefix such as L-alanine or DL-alanine, please see ... Thymidine. *Tímín Thymine. *Tiaimín Thiamine (Vitamin B1). *Triacsin C. *Hormón tíoróidspreagthach Thyroid-stimulating hormone ...
It is commonly found in tRNA, associated with thymidine and cytosine in the TΨC arm and is one of the invariant regions of tRNA ... Pseudouridine kinase. *TRNA-pseudouridine synthase. ReferencesEdit. *^ IUPAC-IUB Commission on Biochemical Nomenclature (1970 ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ...
Other names in common use include pyrimidine ribonucleoside kinase, uridine-cytidine kinase, uridine kinase (phosphorylating), ... I. Uridine-cytidine kinase of Novikoff ascites rat tumor". The Journal of Biological Chemistry. 244 (8): 2204-9. PMID 5782006. ... In enzymology, an uridine kinase (EC 2.7.1.48) is an enzyme that catalyzes the chemical reaction ... Skold O (1960). "Uridine kinase from Erlich ascites tumor: purification and properties". J. Biol. Chem. 235: 3273-3279.. ...
Hamel, W; Magnelli, L; Chiarugi, VP; Israel, MA (June 1996). "Herpes simplex virus thymidine kinase/ganciclovir-mediated ... of the herpes simplex virus thymidine kinase/ganciclovir system in vitro". Gene Ther. 3 (1): 85-92. PMID 8929915.. ... "Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins". Proceedings of the ...
This enzyme is also called galacturonokinase (phosphorylating) D-galacturonic acid kinase. This enzyme participates in ...
... and thymidine to grow.[15] DHFR has also been demonstrated as an enzyme involved in the salvage of tetrahydrobiopterin from ... and then subjected to selective conditions in thymidine-lacking medium. Only the cells with the exogenous DHFR gene along with ...
An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection. ...
... the enzymes phosphoglycerate kinase and pyruvate kinase facilitate the addition of a phosphate group to ADP by way of substrate ...
Adenylate kinase is a specific nucleoside-monophosphate kinase that functions only on adenosine-monophosphate.[1][7] ... Thymidine synthesis first requires reduction of the uridine to deoxyuridine (see next section), before the base can be ... In order to synthesize thymidine, a component of DNA which only exists in the deoxy form, uridine is converted to deoxyuridine ... Pyrimidine nucleotides include cytidine, uridine, and thymidine. The synthesis of any pyrimidine nucleotide begins with the ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ...
Mechanisms of resistance in HSV include deficient viral thymidine kinase, and mutations to viral thymidine kinase and/or DNA ... Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times ... in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated ... into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA ...
... (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme (EC 2.7.3.2) expressed ... Creatine kinase in the blood may be high in health and disease. Exercise increases the outflow of creatine kinase to the blood ... Clinically, creatine kinase is assayed in blood tests as a marker of damage of CK-rich tissue such as in myocardial infarction ... This means creatine kinase in blood may be elevated in a wide range of clinical conditions including the use of medication such ...
Thymidine kinase, Thyroid peroxidase, Tissue transglutaminase, Vitamin K epoxide reductase, Von Willebrand factor ... Amylase, Creatine kinase, Cyclooxygenase, Gastrin, Glucocorticoid, Heme, Histamine, Lactate dehydrogenase, Transglutaminase, ...
Subsequent to the action of TFIIH kinase, Ser2 residues are phosphorylated by CTDK-I in yeast (CDK9 kinase in metazoans). Ctk1 ... "CDK8 cyclin-dependent kinase 8 [Homo sapiens]".. *^ "CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) ... 2002). "A kinase-cyclin pair in the RNA polymerase II holoenzyme". Nature. 374 (6518): 193-6. doi:10.1038/374193a0. PMID ... It has a kinase activity that phosphorylates the C-terminal domain (CTD) of Pol II at the amino acid serine. This switches the ...
티미딘 인산화효소(Thymidine kinase)는 뉴클레오시드 인산화효소 중 하나로 뉴클레오시드 인산화를 담당한다. 아래에서 보이는 것과 같이 ATP 분자에서 인산기를 티미딘에 전달하여 티미딘 일인산(thymidine ... Topolcan, Ondrej; Holubec, Lubos (2008년 2월). "The role of thymidine kinase in cancer diseases". Expert Opinion on Medical ... 유사분열 활성화 단백질 인산화효소(Mitogen-Activated Protein Kinases; MAP kinase; MAPKs)는 세린/트레오닌 인산화효소족으로 다양한 세포외 성장 신호에 반응한다. 성장 호르몬이나 상피성장인자 ... Aufderklamm, S; Todenhöfer, T; Gakis, G; Kruck, S; Hennenlotter, J; Stenzl, A; Schwentner, C (2012년 3월). "Thymidine kinase and ...
A major target of Akt kinases is glycogen synthase kinase-3. EC 2.7.1.37 Pelle. is a serine/threonine kinase that can ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... A serine/threonine protein kinase (EC 2.7.11.1) is a kinase enzyme that phosphorylates the OH group of serine or threonine ( ...
... forming thymidine. Thymidine kinase can then phosphorylate this compound into thymidine monophosphate (TMP). Thymidylate kinase ... Uridine kinase (aka uridine-cytidine kinase) can then phosphorylate this nucleoside into uridine monophosphate (UMP). UMP/CMP ... can phosphorylate TMP into thymidine diphosphate, which nucleoside diphosphate kinase can phosphorylate into thymidine ... Thymidine phosphorylase or pyrimidine-nucleoside phosphorylase adds 2-deoxy-alpha-D-ribose 1-phosphate to thymine, ...
"Deoxyribonucleoside kinases in two aquatic bacteria with high specificity for thymidine and deoxyadenosine". FEMS Microbiology ... Several GST isozymes from various classes have been shown to inhibit the function of a kinase involved in the MAPK pathway that ... regulates cell proliferation and death, preventing the kinase from carrying out its role in facilitating the signaling cascade. ... it is also supported by the fact that the transformed phenotype of tumor cells is associated with aberrantly regulated kinase ...
The transcription terminates after a stretch of four or more thymidines.[2][55] ... Adenylate kinase. *Creatine kinase. Inner membrane. oxidative phosphorylation. *Coenzyme Q - cytochrome c reductase ...
... Tim ONeal and Clayton Smith 07 Contents:. I. Introduction II. General Structure III. ATP ... Finally, thymidine kinase acts catalytically to phosphorylate thymidine , readiying it for further phosphorylation and eventual ... The two subunits of the thymidine kinase dimer each consist of 376 amino acids (Champness et al, 1998) and contain 15 α-helices ... Ganciclovir is a potent HSV TK targeting drug that binds specifically to the viral thymidine kinase in place of dT. (Champness ...
Thymidine kinase 1 Thymidine kinase from herpesvirus Thymidylate kinase Nucleoside-diphosphate kinase Thymidylate synthase ... Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2-deoxythymidine kinase, ATP-thymidine 5-phosphotransferase, ... One difficulty is that the poxvirus thymidine kinase belongs to the same family of thymidine kinases as the human thymidine ... Thymidine kinase 1 is such a salvage enzyme, whereas thymidine kinase 2 and thymidylate synthase are not cell cycle-dependent. ...
In enzymology, an ADP-thymidine kinase (EC 2.7.1.118) is an enzyme that catalyzes the chemical reaction ADP + thymidine ⇌ {\ ... displaystyle \rightleftharpoons } AMP + thymidine 5-phosphate Thus, the two substrates of this enzyme are ADP and thymidine, ... The systematic name of this enzyme class is ADP:thymidine 5-phosphotransferase. Other names in common use include ADP:dThd ... Falke D, Labenz J, Brauer D, Muller WE (1982). "Adenosine diphosphate: thymidine 5-phosphotransferase, a new enzyme activity, ...
... which plays an important role in the making of thymidine triphosphate from thymine -- the only way thymine, cytosine, and oth ... thymidine kinase (thing). See all of thymidine kinase, no other writeups in this node. ... Thymidine kinase is also used as a selectable marker to identify transfected eukaryotic cells. From the BioTech Dictionary at ... cyclin-dependent kinase. transfection. hypoxanthine-guanine phosphoribosyl transferase. nucleic acid. endocytosis. nitrogenous ...
The Effect of Substrate Binding on the Conformation and Structural Stability of Herpes Simplex Virus Type 1 Thymidine Kinase ... Nucleotide and nucleoside kinases Thymidine kinase Herpes simplex virus type 1, different strains [TaxId: 10298] ... Nucleotide and nucleoside kinases Thymidine kinase Herpes simplex virus type 1, different strains [TaxId: 10298] ...
thymidine kinase, cytosolic. Names. cytosolic thymidine kinase. epididymis secretory sperm binding protein. NP_001333592.1. *EC ... TK1 thymidine kinase 1 [Homo sapiens] TK1 thymidine kinase 1 [Homo sapiens]. Gene ID:7083 ... thymidine kinase-1 as a biomarker for CDK4/6 inhibitors. Title: Potential through simplicity: thymidine kinase-1 as a biomarker ... thymidine kinase 1provided by HGNC. Primary source. HGNC:HGNC:11830 See related. Ensembl:ENSG00000167900 MIM:188300 Gene type. ...
The Effect of Substrate Binding on the Conformation and Structural Stability of Herpes Simplex Virus Type 1 Thymidine Kinase ... THYMIDINE KINASE protein, length: 331 (BLAST) Sequence Similarity Cutoff. Rank. Chains in Cluster. Cluster ID / Name. ...
"Thymidine and thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase," ... Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis. Luc Calvin Owono Owono,1,2,3 Melalie ... combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase ... modified thymidines and 5-hydroxymethyl-2′-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors," ...
Thymidine kinaseUniRule annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ... Belongs to the thymidine kinase family.UniRule annotation. ,p>Information which has been generated by the UniProtKB automatic ... ATP + thymidine = ADP + thymidine 5-phosphate.UniRule annotation. ,p>Information which has been generated by the UniProtKB ... tr,B1VAS4,B1VAS4_PHYAS Thymidine kinase OS=Phytoplasma australiense OX=59748 GN=tdk PE=3 SV=1 ...
In vitro transcription of the thymidine kinase gene of herpes simplex virus. G S Read and W C Summers ... In vitro transcription of the thymidine kinase gene of herpes simplex virus ... In vitro transcription of the thymidine kinase gene of herpes simplex virus ... In vitro transcription of the thymidine kinase gene of herpes simplex virus ...
Thymidine kinaseUniRule annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ... Belongs to the thymidine kinase family.UniRule annotation. ,p>Information which has been generated by the UniProtKB automatic ... ATP + thymidine = ADP + thymidine 5-phosphate.UniRule annotation. ,p>Information which has been generated by the UniProtKB ... tr,S5R459,S5R459_9STRE Thymidine kinase OS=Streptococcus lutetiensis 033 GN=tdk PE=3 SV=1 ...
An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene. Anthony Griffiths and Donald M. Coen ... The herpes simplex virus (HSV) gene that encodes thymidine kinase (TK) has long served as a model for studies of eukaryotic ... We have investigated a herpes simplex virus mutant that expresses low levels of thymidine kinase (TK), a phenotype associated ... Abbreviations: HSV, herpes simplex virus; TK, thymidine kinase; IRES, internal ribosome entry site; ACV, acyclovir; ACVr, ACV- ...
Thymidine Kinase 1 overexpression 293T lysate (whole cell) Lysates datasheet (ab94157). Abcam offers quality products including ... All lanes : Anti-Thymidine Kinase 1 antibody (ab57757) at 1/500 dilution. Lane 1 : Thymidine Kinase 1 overexpression 293T ... cell transfected lysate in which Human Thymidine Kinase 1 has been transiently over-expressed using a pCMV-Thymidine Kinase 1 ... Similarity: Belongs to the thymidine kinase family. PTM: Phosphorylated on Ser-13 in mitosis. ...
... consisting of pBR322 linked to the herpes simplex virus type 1 thymidine kinase gene and SV40 genome into thymidine kinase- ... Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX for functional display on the virion. Li, J., Le ... MicroPET imaging of Cre-loxP-mediated conditional activation of a herpes simplex virus type 1 thymidine kinase reporter gene. ... Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. Wildner ...
Knockout Tested Rabbit recombinant monoclonal Thymidine Kinase 1/TK1 antibody [EPR3193]. Validated in WB, IP, IHC, Flow Cyt and ... Anti-Thymidine Kinase 1/TK1 antibody [EPR3193] (Alexa Fluor® 488) (ab201259) *Anti-Thymidine Kinase 1/TK1 antibody [EPR3193] - ... Anti-Thymidine Kinase 1/TK1 antibody [EPR3193]. See all Thymidine Kinase 1/TK1 primary antibodies. ... advise which of the following will specificaly recognize Thymidine Kinase 1 and will not cross react with Thymidine Kinase 2. ...
Protein target information for Thymidine kinase (pig). Find diseases associated with this biological target and compounds ...
... thymidine kinase 1, soluble , thymidine kinase 1 , Thymidine kinase, cytosolic , thymidine kinase , thymidine kinase 1 soluble ... anti-Thymidine Kinase 1, Soluble Antikörper catalyzes the transfer of the terminal phosphate of ATP to thymidine to form ... Thymidine Kinase 1, Soluble (TK1) Antigen-Profil Protein Überblick catalyzes the transfer of the terminal phosphate of ATP to ... anti-Thymidine Kinase 1, Soluble (TK1) (AA 1-234) Antikörper Primary Antibody TK1 Reaktivität: Human ELISA, WB Wirt: Maus ...
Ectopic expression of HHV‐1 thymidine kinase (TK) in the testis of Tg rats increased male infertility. In addition, truncated ... Ectopic Expression of Human Herpesvirus 1 Thymidine Kinase Induces Male Infertility. By Mo Chen, Li‐yi Cai, Takako Kato and ... Ectopic expression of HHV‐1 thymidine kinase (TK) in the testis of Tg rats increased male infertility. In addition, truncated ... Mo Chen, Li‐yi Cai, Takako Kato and Yukio Kato (September 7th 2016). Ectopic Expression of Human Herpesvirus 1 Thymidine Kinase ...
... for thymidine and ATP. The wild-type thymidine kinase has apparent Kms of 0.5 and 20 microM for thymidine and ATP, ... The thymidine kinase encoded by herpes simplex virus type 1 contains an amino acid sequence homologous to a consensus sequence ... Site-directed mutagenesis of a nucleotide-binding domain in HSV-1 thymidine kinase: effects on catalytic activity.. Liu QY1, ... These results indicate that this homologous segment is essential for the function of the thymidine kinase and is involved in ...
Thymidine kinase (TK) is a key enzyme of the salvage pathway that recycles thymidine nucleosides to produce deoxythymidine ... 2012) Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana. ... Efficient Replication of the Plastid Genome Requires an Organellar Thymidine Kinase. Monique Le Ret, Susan Belcher, Stéfanie ... Efficient Replication of the Plastid Genome Requires an Organellar Thymidine Kinase. Monique Le Ret, Susan Belcher, Stéfanie ...
Aims: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an important proliferation marker. We explored the ... Breast cancer, thymidine kinase 1 activity, prediction of recurrence, BRCA1/2 mutation National Category Medical and Health ...
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Systematic literature review using the terms Thymidine kinase 2 deficiency, Thymidine kinase 2 and TK2 from October 2001 ... Thymidine kinase 2 (TK2) is a nuclear-encoded mitochondrial enzyme that catalyses the conversion of deoxycytidine and thymidine ... Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome. Brain 2008;131(Pt 11):2841-50.doi:10.1093/brain/ ... Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration. Hum Mol Genet 2010;19:1669-77.doi: ...
The inhibition is uncompetitive with respect to thymidine, reducing both the apparent Km and Vmax of the enzyme. The inhibition ... Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. ... The inhibition of thymidine kinase in glial tumor cells by an amino sugar, D-glucosamine Cancer Res. 1977 Apr;37(4):1068-74. ... Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. The ...
Compare and order Thymidine Kinase 2, Mitochondrial ELISA Kits. View citations, images, detection ranges, sensitivity, prices ... mt-TK , thymidine kinase 2, mitochondrial , putative deoxyribonucleoside kinase , thymidine kinase 2, mitochondrial S homeolog ... Weitere Produktkategorien zu Thymidine Kinase 2, Mitochondrial ELISA Kit * 5 Thymidine Kinase 2, Mitochondrial ELISA & Assay ... Thymidine Kinase 2, Mitochondrial ELISA Kit. 5 products by 4 suppliers: Abbexa , Biovision , EIAab , USBio ...
In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1 ... In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1 ... Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs.. Clausen, Anders Ranegaard LU ; ... Apparently, deoxyuridine (dU), and not thymidine (dT), is the preferred substrate. We suggest that PmTK1s could be employed as ...
Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma ... Two of the best characterized genes are herpes simplex virus thymidine kinase (TK) gene and Escherichia coli cytosine deaminase ... Hlubinová K, Hlavatý J, Altaner C. Human glioma cells expressing herpes simplex virus thymidine kinase gene treated with ... Combined antitumor effects of an adenoviral cytosine deaminase/thymidine kinase fusion gene in rat C6 glioma. Neurosurgery. ...
Knecht W, Petersen GE, Munch-Petersen B, Piskur J. Deoxyribonucleoside kinases belonging to the thymidine kinase 2 (TK2)-like ... Eriksson S, Wang J. Substrate specificities of mitochondrial thymidine kinase and cytosolic deoxycytidine kinase against 5-aryl ... thymidines and their evaluation as substrates for human thymidine kinases 1 and 2. J Med Chem, 42: 3373-89, 1999. ... thymidines and their biological evaluation as substrates for human thymidine kinases 1 and 2. J Med Chem, 45: 4018-28, 2002. ...
Objectives: Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells ... Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell ...
title = "Structures of thymidine kinase 1 of human and mycoplasma origin",. abstract = "Cytosolic thymidine kinase, TK1, is a ... thymidine kinase 1, cytosolic thymidine kinase, TK1",. author = "Martin Welin and Urszula Kosinska and Nils-Egil Mikkelsen and ... Structures of thymidine kinase 1 of human and mycoplasma origin. I: Proceedings of the National Academy of Science of the ... Structures of thymidine kinase 1 of human and mycoplasma origin. Proceedings of the National Academy of Science of the United ...
  • abstract = "Herpes simplex virus (HSV) mutants defective for thymidine kinase expression (TK-) have been reported to establish latent infection of sensory ganglia of mice, in that HSV latency-associated transcript is expressed, but to be defective for reactivation. (elsevier.com)
  • abstract = "Mouse somatic cells lacking thymidine kinase were mixed in culture with human diploid cells lacking hypoxanthine guanine phosphoribosyl transferase, and hybrid cells were isolated and maintained in a selective medium containing hypoxanthine, aminopterin, and thymidine. (elsevier.com)
  • abstract = "Thymidine kinase I (TK 1 EC. (elsevier.com)
  • abstract = "From a mutagenized population of wild type S49 cells, a clone was isolated in a single step that possessed functional and biochemical deficiencies in both AMP deaminase and thymidine kinase activities. (elsevier.com)
  • abstract = "Trifluridine (FTD), a tri-fluorinated thymidine analogue, is a key component of the oral antitumor drug FTD/TPI (also known as TAS-102), which is used to treat refractory metastatic colorectal cancer. (elsevier.com)
  • The wild-type thymidine kinase has apparent Km's of 0.5 and 20 microM for thymidine and ATP, respectively, while the mutant enzyme displayed Km's of 2.3 and 60 microM for thymidine and ATP. (nih.gov)
  • Revertants of DTB6 cells possessed wild type levels of AMP deaminase activity but remained deficient in thymidine kinase activity, while another revertant of DTB6 cells expressed 11% of the wild type thymidine kinase level but did not perceptibly change its AMP deaminase activity. (elsevier.com)
  • Additionally, kinetic parameters and the ability of these mutants to sensitize tumor cells to GCV in comparison to wild-type thymidine kinase were determined. (openbiochemistryjournal.com)
  • Genes for virus specific thymidine kinases have been identified in Herpes simplex virus, Varicella zoster virus and Epstein-Barr virus. (wikipedia.org)
  • 9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (biomedsearch.com)
  • The genome of the model plant Arabidopsis thaliana has two thymidine kinase genes (AtTK1a and AtTK1b) and microarray data suggest they might have redundant roles. (deepdyve.com)
  • Genes encoding thymidine kinase have been extremely useful as selectable markers for introducing DNA into a number of cells. (ac.ke)
  • This article describes an investigation on the virulence /attenuation of bovine herpesvirus type 5 (BoHV-5) recombinants deleted in the genes encoding glycoprotein E (BoHV-5gEΔ), thymidine kinase (BoHV-5TKΔ), and both gE and TK (BoHV-5gEΔTKΔ). (bvsalud.org)
  • Ganciclovir is a potent HSV TK targeting drug that binds specifically to the viral thymidine kinase in place of dT. (kenyon.edu)
  • The present study aimed to examine the apoptotic effects of adenovirus (ADV)‑mediated herpes simplex virus thymidine kinase (ADV‑TK) combined with ganciclovir (GCV) in tissues obtained from patients with hepatocellular carcinoma in order to provide a theoretical basis for the development of this gene therapy program. (spandidos-publications.com)
  • Gene-mediated cytotoxic immunotherapy (GMCI) is a clinical intervention that forms a tumor-specific vaccine effect via intratumoral delivery of adenovirus (ADV)-mediated herpes simplex virus thymidine kinase (ADV-TK) followed by a systemic anti-herpetic prodrug, such as valacyclovir or ganciclovir (GCV), in combination with standard tumor resection surgery or radiation ( 7 ). (spandidos-publications.com)
  • Herpes simplex virus thymidine kinase (HSV-tk) converts ganciclovir (GCV) into an active compound, which can be incorporated into DNA molecules and terminate DNA synthesis. (cun.es)
  • We evaluated the interaction between oncolytic, replication-competent adenoviral vectors and the herpes simplex virus-1 thymidine kinase (HSV1-tk) gene/ganciclovir (GCV) suicide system for the treatment of malignant gliomas. (eur.nl)
  • Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) is an extensively studied form of cytotoxic gene therapies. (eurekaselect.com)
  • Ann-Marie Maatta, Haritha Samaranayake, Jere Pikkarainen, Thomas Wirth and Seppo Yla-Herttuala, " Adenovirus Mediated Herpes Simplex Virus-Thymidine Kinase/Ganciclovir Gene Therapy for Resectable Malignant Glioma", Current Gene Therapy (2009) 9: 356. (eurekaselect.com)
  • First, using the herpes simplex virus 1 thymidine kinase/ ganciclovir (HSV-tk/GCV) gene therapy approach, we investigated 4-PB for its effect on HSV-tk gene expression and the bystander effect in glioma cell cultures. (ki.se)
  • Ovarian cancer gene therapy: repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model. (scienceexchange.com)
  • OBJECTIVE Our purpose was to assess the effect of multiple injections of the system of herpes simplex virus thymidine kinase in an adenovirus vector and ganciclovir on survival in a murine model of human epithelial ovarian cancer. (scienceexchange.com)
  • STUDY DESIGN In this work we tested the ability of the system of thymidine kinase delivered by an adenovirus vector and ganciclovir to treat ovarian cancer in a novel murine model for epithelial ovarian cancer, SaskMouse. (scienceexchange.com)
  • RESULTS The system of thymidine kinase delivered by an adenovirus vector and ganciclovir was applied to SaskMouse. (scienceexchange.com)
  • Survivals were 23 +/- 2, 27 +/- 2, and 35 +/- 4 days, respectively (P CONCLUSIONOur data suggest that multiple intraperitoneal injections of the combination of thymidine kinase delivered by an adenovirus vector and ganciclovir are effective in prolonging survival in the presence of ovarian cancer. (scienceexchange.com)
  • More than 95% of the vincristine-resistant cells transfected or transduced with pHa-MDR-IRES-TK showed hypersensitivity to ganciclovir, which selects against cells expressing herpes simplex virus thymidine kinase. (elsevier.com)
  • The altered active site architecture may also account for the differences in the substrate activity of ganciclovir for the two thymidine kinases. (ox.ac.uk)
  • Herpes simplex virus type 1 (HSV) thymidine kinase (TK) has been widely used in suicide gene therapy for the treatment of cancer due to its broad substrate specificity and the inability of the endogenous human TK to phosphorylate guanosine analogs such as ganciclovir (GCV). (openbiochemistryjournal.com)
  • catalyzes the transfer of the terminal phosphate of ATP to thymidine to form thymidine 5'-phosphate (dTMP). (antikoerper-online.de)
  • TK1 catalyzes the conversion of thymidine to deoxythymidine monophosphate (dTMP), which is further phosphorylated to di (dTDP) and triphosphates (dTTP) prior to being incorporated into DNA [ 2 ]. (biomedcentral.com)
  • Curiously, these parasites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second via thymidylate synthase-dihydrofolate reductase. (umn.edu)
  • Thymidine kinase (EC 2.7.1.21) is the key enzyme in the pyrimidine salvage pathway catalyzing the transfer of the phosphate from ATP to thymidine to produce dTMP. (ijcmas.com)
  • This is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. (ruc.dk)
  • The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases indicating a different evolutionary origin. (ruc.dk)
  • The viral thymidine kinases differ completely from the mammalian enzymes both structurally and biochemically and are inhibited by inhibitors that do not inhibit the mammalian enzymes. (wikipedia.org)
  • Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells metabolism and proliferation. (nih.gov)
  • Thymidine kinase (TK) belongs to a group of enzymes such as dihydrofolate reductase, thymidylate synthase, and DNA polymerase that are involved in DNA synthesis and precursor production. (acris-antibodies.com)
  • Thymidine kinases are key enzymes in the salvage pathway of TdR synthesis and have been the targets for designing nucleoside analogues for monitoring cellular proliferation. (usc.edu)
  • TS and thymidine phosphorylase (TP) are key enzymes of the pyrimidine salvage pathway. (aspetjournals.org)
  • 1. Thyroparathyroidectomy (TPTX) carried out at 72 h before partial hepatectomy (PH) reduced the induction of hepatic thymidylate synthetase (TS) and thymidine kinase (TK), which are rate-determining enzymes in DNA synthesis, at 24 h after PH. (clinsci.org)
  • These results strongly suggest that the loss of thymidine kinase activity in the extramitochondrial compartment of LM(TK-) Cl 1D cells has not been accompanied by the loss of the mitochondria-associated enzyme activity, pointing to a different genetic or epigenetic control of the extramitochondrial and mitochondrial enzymes. (caltech.edu)
  • The selectivity of ACV as an antiherpesvirus drug is based on its specific interaction with virus-encoded enzymes, thymidine kinase (TK) and DNA polymerase (DNA Pol). (asm.org)
  • In addition, a striking close correlation was found between the inhibitory activities of the test compounds against TK-2 and Mycobacterium tuberculosis thymidylate kinase that is strongly indicative of close structural and/or functional similarities between both enzymes in relation to their mode of interaction with these nucleoside analog inhibitors. (ugent.be)
  • Thymidine kinase (TK) belongs to the group of oncofetal enzymes. (immunotech.cz)
  • The hybrid cells have only mouse electrophoretic variants for glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase, suggesting that the human genetic loci for these enzymes are not represented in the hybrid genome and may be unlinked to that for thymidine kinase. (elsevier.com)
  • Such viral thymidine kinases (tk), beside having a broader substrate specificity compared with host cell enzymes, also show significant variation in nucleoside phosphorylation among themselves. (ox.ac.uk)
  • Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21. (wikipedia.org)
  • The cell line LM(TK-) Cl 1D, a derivative of mouse L fibroblasts deficient in thymidine kinase (EC 2.7.1.21) that shows very little thymidine kinase activity in extracts of whole cells as compared to the parental line, and that does not incorporate thymidine or 5-bromodeoxyuridine into nuclear DNA, has maintained the capacity to incorporate these precursors into mitochondrial DNA at a substantial rate. (caltech.edu)
  • talks.cam : Can serum thymidine kinase activity differentiate canine IBD and GI lymphoma? (cam.ac.uk)
  • Serum thymidine kinase 1 (TK1) activity determination is used as marker for tumor monitoring in both human and veterinary medicine. (slu.se)
  • A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphoma. (semanticscholar.org)
  • In this study, a human mitochondrial thymidine kinase (hTK2) was expressed in an attempt to characterize in detail its kinetic parameters. (usc.edu)
  • Munch-Petersen, B 2010, ' Enzymatic Regulation of Cytosolic Thymidine Kinase 1 and Mitochondrial Thymidine Kinase 2: A Mini Review ', Nucleosides, Nucleotides and Nucleic Acids , vol. 29, no. 4-6, pp. 363-369. (ruc.dk)
  • Human mitochondrial thymidine kinase is selecti. (ugent.be)
  • It has been suggested that the antiviral and anti-cancer activity of thymidine analogues is, at least partly, achieved by down-regulation of mitochondrial thymidine kinase. (schwenkreis.com)
  • As the purpose of this protein is to phosphorylate an unphosphorylated thymidine (dT), one of the most important abilities of TK is its ability to bind ATP as a substrate and eventally catalyze the transfer of a phosphate group from ATP to thymidine. (kenyon.edu)
  • The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. (nih.gov)
  • Stimulation of T cell proliferation and the production of inflammatory cytokines may be induced by herpes simplex virus type 1 thymidine kinase (HSV-TK) protein, which has been described to resemble a super-antigen molecule ( 7 ). (spandidos-publications.com)
  • Cisplatin could increase the phosphorylation of mitogen-activated protein kinase kinase 1/2 (MKK1/2)-extracellular signal-regulated kinase 1/2 (ERK1/2) and the protein levels of TS and TP through enhancing the protein stability in A549 and H1975 cells. (aspetjournals.org)
  • The kinetics for activation of the cyclic adenosine 3′:5′-monophosphate (cyclic AMP)-dependent protein kinase (PKA) and thymidine incorporation into DNA was investigated in epinephrine- and prostaglandin E 1 (PGE 1 )-treated murine P1798 lymphosarcoma cells. (aacrjournals.org)
  • We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. (ucl.ac.uk)
  • Semisynthesis of human thymidine monophosphate kinase Protein semisynthesis based on native chemical ligation has become a major protein engineering tool that allows manipulation of domains of proteins of all sizes. (schwenkreis.com)
  • To reduce the levels of recombinant protein expression in comparison with the commonly used, very strong CMV promoter, the herpes simplex virus thymidine kinase (TK) gene promoter, and mutants thereof were analyzed. (nuigalway.ie)
  • About two-thirds of the mutations that cause this condition change single protein building blocks (amino acids) in thymidine kinase 2. (nih.gov)
  • Frankie Gardner from Palm Desert was looking for semisynthesis of human thymidine monophosphate kinase Kristopher Burke found the answer to a search query semisynthesis of human thymidine monophosphate kinase Link semisynthesis of human thymidine monophosphate kinase schwenkreis.com should application essays. (schwenkreis.com)
  • Cytosolic thymidine kinase, TK1, is a well-known cell cycle regulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs as AZT. (ruc.dk)
  • In recent years, development of PET radiotracer has focused on thymidine (TdR) analogs for imaging cell proliferation that are resistant to metabolism in vivo. (usc.edu)
  • The ability to isolate single step mutants with two seemingly independent biochemical abnormalities raises the speculation that there may be some link between cellular functions responsible for purine nucleotide and thymidine metabolism. (elsevier.com)
  • Thymidine kinase is an enzyme involved in DNA precursor metabolism and DNA replication. (ac.ke)
  • The inhibition is uncompetitive with respect to thymidine, reducing both the apparent Km and Vmax of the enzyme. (nih.gov)
  • The addition of D-glucosamine or its metabolites to cell-free thymidine kinase produced an inhibition which differed quantitatively and qualitatively from that which resulted from treatment of intact cells with D-glucosamine. (nih.gov)
  • The magnitude of inhibition of thymidine kinase activity and amino acid incorporation by D-glucosamine was comparable to that produced by cycloheximide, suggesting that the inhibition might arise from interference with enzyme synthesis. (nih.gov)
  • However, whereas the kinetics of recovery of amino acid incorporation from inhibition was rapid, thymidine kinase activity was depressed for at least 6 hr after drug washout. (nih.gov)
  • These compounds showed partial competitive inhibition for thymidine phosphorylation by TK1. (aacrjournals.org)
  • A positive correlation between the duration and extent of PKA activation and Accumulation of cyclic AMP and inhibition of thymidine incorporation into DNA was observed with both hormones. (aacrjournals.org)
  • All hormone concentrations which increased cyclic AMP accumulation also promoted inhibition of thymidine incorporation into DNA. (aacrjournals.org)
  • Thymidine kinase (TK) activity decreased under these conditions with 50% inhibition achieved within approximately 8 h. (elsevier.com)
  • The results presented are best explained by assuming either that two forms of thymidine kinase are present in rat C6 cells and are differently affected by D-glucosamine or that D-glucosamine acts by two separate mechanisms to inhibit a single form of the enzyme. (nih.gov)
  • Two forms of thymidine kinase with native molecular masses of 59 kDa and 80 kDa have been identified and purified 6800- and 4600-fold, respectively. (ac.ke)
  • Fingerprint Dive into the research topics of 'AMP deaminase and thymidine kinase deficiencies in a mutant mouse S49 cell clone. (elsevier.com)
  • Synthesis and biological evaluation of bicyclic nucleosides as inhibitors of M. tuberculosis thymidylate kinase," ChemMedChem , vol. 1, no. 10, pp. 1081-1090, 2006. (hindawi.com)
  • Thymidine kinase (TK) is a key enzyme of the salvage pathway that recycles thymidine nucleosides to produce deoxythymidine triphosphate. (plantphysiol.org)
  • Surprisingly, the antiparasitic nucleosides AraT, AraC, and IDC are not substrates for CpTK, indicating that Cryptosporidium possesses another deoxynucleoside kinase. (umn.edu)
  • The use of thymidine (TdR) and thymidine analogs such as 3′-deoxy-3′-fluorothymidine (FLT) as positron emission tomography (PET)-based tracers of tumor proliferation rate is based on the hypothesis that measurement of uptake of these nucleosides, a function primarily of thymidine kinase-1 (TK 1 ) activity, provides an accurate measure of cell proliferation in tumors. (elsevier.com)
  • We describe here an alternative approach using the Epstein-Barr virus (EBV) encoded thymidine kinase (TK) to directly phosphorylate adducted nucleosides to give the [5'-32P]monophosphates. (openrepository.com)
  • Potential through simplicity: thymidine kinase-1 as a biomarker for CDK4/6 inhibitors. (nih.gov)
  • Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase: new insights into the phosphoryl transfer mechanism," Journal of Biological Chemistry , vol. 278, no. 7, pp. 4963-4971, 2003. (hindawi.com)
  • Vanheusden V, Van Rompaey P, MUNIER-LEHMANN H, POCHET S, HERDEWIJN P, Van Calenbergh S. Thymidine and thymidine-5 '-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. (ugent.be)
  • Interaction of α-Thymidine Inhibitors with Thymidylate Kinase. (mysciencework.com)
  • We transcribed in vitro a cloned 3.5-kilobase fragment of herpes simplex virus type 1 DNA that contains the gene for the viral thymidine kinase. (pnas.org)
  • Thymidine analogs containing o -carboranylalkyl groups at the 3-position were screened as potential substrates for human thymidine kinase 1 (TK1), an enzyme that is selectively expressed in a variety of rapidly proliferating cells, including tumor cells. (aacrjournals.org)
  • The thymidine analogue 3'-deoxy-3'-[18F]-fluorothymidine ([18F]FLT) is used to image tumour proliferation by positron emission tomography (PET). (bl.uk)
  • Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs. (lu.se)
  • Chemical structures of thymidine kinase substrate analogs AZT.Publications. (schwenkreis.com)
  • These results indicate that this homologous segment is essential for the function of the thymidine kinase and is involved in the substrate binding domain of the enzyme. (nih.gov)
  • Neither compound was a substrate of recombinant human thymidine phosphorylase nor were their respective 5′-monophosphates substrates of 5′-deoxynucleotidase 1, thereby indicating potential in vivo stability. (aacrjournals.org)
  • In respect to the phosphate acceptor the enzyme showed sharp specificity: it used as a substrate only thymidine, deoxyuridine and its derivatives, substituted at the 5-th position by haloid group. (msk.ru)
  • Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir. (expasy.org)
  • The salvage pathway recycles nucleotides by converting deoxynucleosides into the corresponding nucleotides by the action of nucleotide kinases. (plantphysiol.org)
  • Thymidine kinase (TK) is a crucial enzyme in the pyrimidine salvage pathway. (plantphysiol.org)
  • TK is responsible for catalyzing the phosphorylation of thymidine, which functions as a part of the pyrimidine salvage pathway involved in DNA synthesis. (acris-antibodies.com)
  • To be retained in cells, [18F]FLT is phosphorylated by thymidine kinase 1 (TK1), the first enzyme in the salvage pathway for DNA synthesis, and for this reason the cellular incorporation of [18F]FLT is dependent on TK1 activity. (bl.uk)
  • Plasencia, Javier 2014-12-24 00:00:00 Thymidine kinase catalyzes the first step in the nucleotide salvage pathway by transferring a phosphate group to a thymidine molecule. (deepdyve.com)
  • Thymidine kinase 1 (TK1) is one of these proliferation biomarkers and is involved in the salvage pathway of DNA precursor synthesis. (biomedcentral.com)
  • TK1 is a dNs kinase involved in the utilization of thymidine as a part of the salvage pathway. (arocell.com)
  • Thymidine Kinase 1 is involved in the DNA synthesis via the metabolic salvage pathway. (arocell.com)
  • Thymidine kinase catalyzes the reaction: Thd + ATP → TMP + ADP where Thd is (deoxy)thymidine, ATP is adenosine triphosphate, TMP is (deoxy)thymidine monophosphate and ADP is adenosine diphosphate. (wikipedia.org)
  • Other names in common use include ADP:dThd phosphotransferase, and adenosine diphosphate-thymidine phosphotransferase. (wikipedia.org)
  • Thymidine kinase catalyses the reaction: Thd + ATP = TMP + ADP, where Thd is deoxythymidine , ATP is (energy-rich) adenosine 5'-triphosphate, TMP is deoxythymidine 5'-phosphate and ADP is adenosine 5'-diphosphate. (chemeurope.com)
  • Our results suggest that thymidine kinase contributes to several DNA repair pathways by providing deoxythymidine triphosphate that serve as precursors for DNA repair and to balance deoxyribonucleotides pools. (deepdyve.com)
  • The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin's lymphoma. (semanticscholar.org)
  • 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.75. (chemeurope.com)
  • Deoxythymidine monophosphate, the product of the reaction catalysed by thymidine kinase, is in turn phosphorylated to deoxythymidine diphosphate and further to deoxythymidine triphosphate. (chemeurope.com)
  • Deoxythymidine monophosphate is produced by the cell in two different reactions - either by phosphorylation of deoxythymidine as described above or by methylation of deoxyuridine monophosphate - that is a product of other metabolic pathways unrelated to thymidine. (chemeurope.com)
  • The thymidine kinase encoded by herpes simplex virus type 1 contains an amino acid sequence homologous to a consensus sequence related to the ATP-binding site in many proteins. (nih.gov)
  • Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. (biomedsearch.com)
  • Mutations in the thymidine kinase gene ( tk ) of herpes simplex virus type 1 (HSV-1) explain most cases of virus resistance to acyclovir (ACV) treatment. (asm.org)
  • Substituted 3'-thiourea derivatives of beta-thymidine (dThd) and 5'-thiourea derivatives of alpha-dThd have been evaluated for their inhibitory activity against recombinant human cytosolic dThd kinase-1 (TK-1), human mitochondrial TK-2, herpes simplex virus type 1 (HSV-1) TK, and varicella-zoster virus TK. (ugent.be)
  • A series of selective antiherpetic compounds were found to exert pronounced cytostatic activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) thymidine kinase (TK) gene-transfected mammary carcinoma FM3A cells. (kuleuven.be)
  • We engineered T cells to express CD19-specific CAR, firefly luciferase (ffLuc), and herpes simplex virus type-1 thymidine kinase (TK) using the non-viral-based Sleeping Beauty (SB) transposon/transposase system adapted for human application. (springermedizin.de)
  • The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter. (ucl.ac.uk)
  • We have compared isogenic recA13/recA + Escherichia coli K-12 strains for the induction by N-ethylN-nitrosourea (ENU) of forward mutations at a plasmid-encoded herpes simplex virus type 1 thymidine kinase (HSV-tk) gene. (elsevier.com)
  • The hybrid plasmid pTK1 consists of the herpes simplex virus type 1 (HSV-1) Bam HI p fragment, which contains the thymidine kinase (TK) gene, inserted into the vector pAT 153. (microbiologyresearch.org)
  • The gene for the thymidine kinase (TK) of Herpes simplex virus type 1 (HSV-1) is located in the KpnI m and BamHI p fragments of the genome (Wigler et al. (scripps.edu)
  • In enzymology, an ADP-thymidine kinase (EC 2.7.1.118) is an enzyme that catalyzes the chemical reaction ADP + thymidine ⇌ {\displaystyle \rightleftharpoons } AMP + thymidine 5'-phosphate Thus, the two substrates of this enzyme are ADP and thymidine, whereas its two products are AMP and thymidine 5'-phosphate. (wikipedia.org)
  • They can be phosphorylated to their corresponding 5′-monophosphates by thymidine kinase 1 (TK1), a cytosolic enzyme that catalyzes the transfer of γ-phosphate group from ATP to the 5′-hydroxyl group of dThd and deoxyuridine. (aacrjournals.org)
  • It catalyzes thymidine transformation to thymidine monophosphate in the presence of ATP. (immunotech.cz)
  • There is a feed-back regulation of the action of thymidine kinase in the cell: thymidine triphosphate (TTP), the product of the further phosphorylation of thymidine, acts as an inhibitor to thymidine kinase. (wikipedia.org)
  • The overall phosphorylation of thymidine to thymidine triphosphate does not follow Michaelis-Menten kinetics, and the various phosphates of thymidine and uridine interfere with the phosphorylation of each other. (wikipedia.org)
  • An enzyme (abbreviated tk ) which plays an important role in the making of thymidine triphosphate from thymine -- the only way thymine , cytosine , and other pyrimidine molecule s are able to become part of nucleic acid s. (everything2.com)
  • From this study, (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine emerged as a promising candidate compound for the treatment of HSV-1 TK gene-transfected tumors in vivo, due to its metabolic stability (i.e., resistance to hydrolysis by thymidine phosphorylase). (kuleuven.be)
  • Plasmodium falciparum thymidylate kinase (PfTMK) is a critical enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. (mysciencework.com)
  • Finally and most importantly, we present here, the tomato thymidine kinase 1 (ToTK1) from its identification and characterization to its in vitro and in vivo testing as a suicide gene. (ki.se)
  • Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy. (nih.gov)
  • Site-directed mutagenesis of a nucleotide-binding domain in HSV-1 thymidine kinase: effects on catalytic activity. (nih.gov)
  • Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. (nih.gov)
  • Substituted 3'-thiourea derivatives of beta-thymidine (dThd) and 5'-thiourea derivatives of alpha-dThd have been evaluated for their inhibitory activity against recombinant human cytosolic dThd kin. (ugent.be)
  • Thymidine kinase 1 (TK1) is a cellular enzyme involved in DNA precursor synthesis, and its activity has been used as a proliferation marker for monitoring malignant diseases. (biomedcentral.com)
  • Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients. (semanticscholar.org)
  • However, after long-term propagation in the selective medium this chromosome has been lost, although cells continue to show thymidine kinase activity as demonstrated by the incorporation of 3 H-thymidine into DNA in the hybrid cell. (elsevier.com)
  • Migeon, BR & Miller, CS 1968, ' Human-mouse somatic cell hybrids with single human chromosome (group E): Link with thymidine kinase activity ', Science , vol. 162, no. 3857, pp. 1005-1006. (elsevier.com)
  • Tissue extracts of epithelial ovarian carcinomas (N = 7) and normal ovaries (N=9) were analyzed for thymidine kinase activity using the polyethyleneimine-cellulose disc radioassay. (elsevier.com)
  • Second, DTB6 cells possessed a virtual complete deficiency in thymidine kinase activity. (elsevier.com)
  • Anticancer activity of a thymidine quinoxaline conjugate is modulated by cytosolic thymidine pathways. (abcam.cn)
  • Reversal of the antimicrobial activity of trimethoprim by thymidine in commercially prepared media. (microbiologyresearch.org)
  • Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. (wjgnet.com)
  • To determine whether the hybrid promoter could elicit RMS-specific cytotoxicity, a mammalian expression vector containing the herpes simplex virus thymidine kinase (HSV tk) under control of the hybrid myo D enhancer/SV40 promoter was constructed. (aspetjournals.org)
  • We have also investigated whether an adenoviral cytomegalovirus-thymidine kinase (Tk) vector might induce an antitumoral effect in this model. (cun.es)
  • Expression from an internal AUG codon of herpes simplex thymidine kinase gene inserted in a retrovirus vector. (asm.org)
  • We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). (elsevier.com)
  • This System was used to develop a new retroviral vector pHa-MDR-IRES-TK which expresses a single mRNA from which translation of the MDRl gene is cap dependent and translation of the herpes simplex virus thymidine kinase gene is IRES dependent The pHa-MDR-IRES-TK transfectants showed high levels of P-glycoprotein expression and multidrug resistance. (elsevier.com)
  • Sugimoto, Y , Aksentijevich, I & Gottesman, MM 1995, ' Coexpression of a Multidrug-resistance Gene(MDR1) and Herpes Simplex Virus Thymidine Kinase Gene as Part of a Bicistronic Messenger RNA in a Retrovirus Vector Allows Selective Killing of MDR1-transduced Cells ', Clinical Cancer Research , vol. 1, no. 4, pp. 447-457. (elsevier.com)
  • Thymidine Kinase: diagnostic and prognostic potential. (arocell.com)
  • Hay, Kathleen A. / Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by nucleoside . (elsevier.com)
  • Herpes virus thymidine kinases are responsible for the activation of nucleoside antiviral drugs including (E)-5-(2-bromovinyl)-2'-deoxyuridine. (ox.ac.uk)
  • Thymidine kinases have a key function in the synthesis of DNA and therefore in cell division, as they are part of the unique reaction chain to introduce thymidine into the DNA. (wikipedia.org)
  • Aims: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an important proliferation marker. (diva-portal.org)
  • Apart from the complex de novo synthesis of dTTP through UDP reduction, dTTP is provided through salvage of thymidine catalyzed by the thymidine kinases, the cytosolic and cell cycle regulated TK1 and the mitochondrial and constitutively expressed TK2. (ruc.dk)
  • After fusion, the cells are grown in a medium with methotrexate [87] or aminopterin [88] that inhibit the enzyme dihydrofolate reductase thus blocking the de novo synthesis of thymidine monophosphate. (schwenkreis.com)
  • Thymidine Kinase 1 (TK1) is a key enzyme in DNA precursor synthesis. (arocell.com)
  • Thymidine Kinases are coupling a phosphate group from ATP to thymidine as part of the DNA synthesis and repair machinery in all living cells. (arocell.com)
  • Ectopic expression of HHV‐1 thymidine kinase (TK) in the testis of Tg rats increased male infertility. (intechopen.com)
  • The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. (ucl.ac.uk)
  • Thymidine Kinase 1, Soluble (TK1) Antibody Pair for use in Sandwich ELISA Assay development. (abbexa.com)
  • Interconversion of nucleotide di- and triphosphates / Thymidylate kinase signature. (pdbj.org)
  • Thymidine Kinase 1, Soluble (TK1) standard. (abbexa.com)
  • Synergistic effects on ganglionic herpes simplex virus infections by mutations or drugs that inhibit the viral polymerase and thymidine kinase. (harvard.edu)
  • Natural polymorphism map (to scale) of thymidine kinase (TK) (A) and DNA polymerase (B) among HSV-1 and HSV-2 strains. (asm.org)
  • Two different classes of thymidine kinases have been identified and are included in this super family: one family groups together thymidine kinase from herpesvirus as well as cellular thymidylate kinases, the second family groups TK from various sources that include, vertebrates, bacteria, the bacteriophage T4, poxviruses, African swine fever virus (ASFV) and Fish lymphocystis disease virus (FLDV). (wikipedia.org)
  • Clinical Applicability of the Proliferation Marker Thymidine Kinase 1 in Head and Neck Cancer Patients. (nih.gov)
  • Zhang J, Jia Q, Zou S, Zhang P, Zhang X, Skog S, Luo P, Zhang W and He Q: Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients. (spandidos-publications.com)
  • The proliferation marker thymidine kinase 1 in clinical use. (semanticscholar.org)
  • The thymidine kinase level in serum therefore serves as a measure of malignant proliferation, indirectly as a measure of the aggressivity of the tumor. (schwenkreis.com)
  • In mammals thymidine kinase supplies deoxyribonucleotides for DNA replication and DNA repair, and the expression of the gene is tightly regulated during the cell cycle. (deepdyve.com)
  • In order to study cell cycle regulation of thymidine kinase, the gene which encodes this enzyme, as well as aspects 'of DNA replication in the ciliated protozoan Tetrahymena thermophila, we have purified thymidine kinase from Tetrahymena. (ac.ke)
  • Chen Y-L, Eriksson S, Chang Z-F. Regulation and functional contribution of Thymidine Kinase 1 in repair of DNA damage. (arocell.com)
  • Regulation of human Thymidine Kinase during the cell cycle. (arocell.com)
  • The regulation of Thymidine Kinase in HL-60 human promyeloleukemia cells. (arocell.com)
  • In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1), was identified. (lu.se)
  • The systematic name of this enzyme class is ADP:thymidine 5'-phosphotransferase. (wikipedia.org)