Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Caspase 10: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Caspases, Initiator: A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Oligopeptides: Peptides composed of between two and twelve amino acids.Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Line: Established cell cultures that have the potential to propagate indefinitely.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Caspases, Effector: A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.CRADD Signaling Adaptor Protein: A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.CARD Signaling Adaptor Proteins: A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Receptor-Interacting Protein Serine-Threonine Kinases: A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.JNK Mitogen-Activated Protein Kinases: 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.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Mice, Inbred C57BLCeramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Receptor-Interacting Protein Serine-Threonine Kinase 2: A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Receptors, Tumor Necrosis Factor, Type I: A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Acetylcysteine: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Viral Proteins: Proteins found in any species of virus.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Endoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Deoxyadenine Nucleotides: Adenine nucleotides which contain deoxyribose as the sugar moiety.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Insect Proteins: Proteins found in any species of insect.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.FlavoproteinsCathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bongkrekic Acid: An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.Pentanoic AcidsHepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Protein Kinase C-delta: 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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Lamin Type B: A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.Isatin: An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.Keratin-18: A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)

Inhibition of NF-kappa B activity in human T lymphocytes induces caspase-dependent apoptosis without detectable activation of caspase-1 and -3. (1/222)

NF-kappa B is involved in the transcriptional control of various genes that act as extrinsic and intrinsic survival factors for T cells. Our findings show that suppression of NF-kappa B activity with cell-permeable SN50 peptide, which masks the nuclear localization sequence of NF-kappa B1 dimers and prevents their nuclear localization, induces apoptosis in resting normal human PBL. Inhibition of NF-kappa B resulted in the externalization of phosphatidylserine, induction of DNA breaks, and morphological changes consistent with apoptosis. DNA fragmentation was efficiently blocked by the caspase inhibitor Z-VAD-fmk and partially blocked by Ac-DEVD-fmk, suggesting that SN50-mediated apoptosis is caspase-dependent. Interestingly, apoptosis induced by NF-kappa B suppression, in contrast to that induced by TPEN (N,N,N',N'-tetrakis [2-pyridylmethyl]ethylenediamine) or soluble Fas ligand (CD95), was observed in the absence of active death effector proteases caspase-1-like (IL-1 converting enzyme), caspase-3-like (CPP32/Yama/apopain), and caspase-6-like and without cleavage of caspase-3 substrates poly(ADP-ribose) polymerase and DNA fragmentation factor-45. These findings suggest either low level of activation is required or that different caspases are involved. Preactivation of T cells resulting in NF-kappa B nuclear translocation protected cells from SN50-induced apoptosis. Our findings demonstrate an essential role of NF-kappa B in survival of naive PBL.  (+info)

Alternative, non-secretase processing of Alzheimer's beta-amyloid precursor protein during apoptosis by caspase-6 and -8. (2/222)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Although the pathogenesis of AD is unknown, it is widely accepted that AD is caused by extracellular accumulation of a neurotoxic peptide, known as Abeta. Mutations in the beta-amyloid precursor protein (APP), from which Abeta arises by proteolysis, are associated with some forms of familial AD (FAD) and result in increased Abeta production. Two other FAD genes, presenilin-1 and -2, have also been shown to regulate Abeta production; however, studies examining the biological role of these FAD genes suggest an alternative theory for the pathogenesis of AD. In fact, all three genes have been shown to regulate programmed cell death, hinting at the possibility that dysregulation of apoptosis plays a primary role in causing neuronal loss in AD. In an attempt to reconcile these two hypotheses, we investigated APP processing during apoptosis and found that APP is processed by the cell death proteases caspase-6 and -8. APP is cleaved by caspases in the intracellular portion of the protein, in a site distinct from those processed by secretases. Moreover, it represents a general effect of apoptosis, because it occurs during cell death induced by several stimuli both in T cells and in neuronal cells.  (+info)

Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. (3/222)

Neuronal cell death, neurofibrillary tangles, and amyloid beta peptide (Abeta) deposition depict Alzheimer's disease (AD) pathology, but neuronal loss correlates best with dementia. We have shown that increased production of Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing. Here, we investigate key effectors of cell death, caspases, in human neuronal apoptosis and APP processing. We find that caspase-6 is activated and responsible for neuronal apoptosis by serum deprivation. Caspase-6 activity precedes the time of commitment to neuronal apoptosis by 10 h, indicating possible activity without subsequent apoptosis. Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Abeta. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Abeta-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons. A pulse-chase experiment reveals a precursor-product relationship between Capp6.5, intracellular Abeta, and secreted Abeta, indicating a potential alternate amyloidogenic pathway. Caspase-6 proenzyme is present in adult human brain tissue, and the p10 active caspase-6 fragment is detected in AD brain tissue. These results indicate a possible alternate pathway for APP amyloidogenic processing in human neurons and a potential implication for this pathway in the neuronal demise of AD.  (+info)

Cleavage and inactivation of ATM during apoptosis. (4/222)

The activation of the cysteine proteases with aspartate specificity, termed caspases, is of fundamental importance for the execution of programmed cell death. These proteases are highly specific in their action and activate or inhibit a variety of key protein molecules in the cell. Here, we study the effect of apoptosis on the integrity of two proteins that have critical roles in DNA damage signalling, cell cycle checkpoint controls, and genome maintenance-the product of the gene defective in ataxia telangiectasia, ATM, and the related protein ATR. We find that ATM but not ATR is specifically cleaved in cells induced to undergo apoptosis by a variety of stimuli. We establish that ATM cleavage in vivo is dependent on caspases, reveal that ATM is an efficient substrate for caspase 3 but not caspase 6 in vitro, and show that the in vitro caspase 3 cleavage pattern mirrors that in cells undergoing apoptosis. Strikingly, apoptotic cleavage of ATM in vivo abrogates its protein kinase activity against p53 but has no apparent effect on the DNA binding properties of ATM. These data suggest that the cleavage of ATM during apoptosis generates a kinase-inactive protein that acts, through its DNA binding ability, in a trans-dominant-negative fashion to prevent DNA repair and DNA damage signalling.  (+info)

Proteolytic cleavage of beta-catenin by caspases: an in vitro analysis. (5/222)

Cleavage of structural proteins by caspases has been associated with the severe morphological changes occurring during the apoptotic process. One of the proteins regulating the connection of the actin filament with cadherins in a cell-cell adhesion complex is beta-catenin. During apoptosis, both an N-terminal and a small C-terminal part are removed from beta-catenin. Removal of the N-terminal part may result in a disconnection of the actin filament from a cadherin cell-cell adhesion complex. We demonstrate that caspase-8, -3 and -6 directly proteolyse beta-catenin in vitro. However, the beta-catenin cleavage products generated by caspase-8 were different from those generated by caspase-3 or caspase-6. Caspase-1, -2, -4/11 and -7 did not or only very inefficiently cleave beta-catenin. These data suggest that activation of procaspase-3, -6 or -8 by different stimuli in the cell might result in a differential proteolysis of beta-catenin.  (+info)

Caspase-induced proteolysis of the cyclin-dependent kinase inhibitor p27Kip1 mediates its anti-apoptotic activity. (6/222)

The caspase-mediated cleavage of a limited number of cellular proteins is a common feature of apoptotic cell death. This cleavage usually inhibits the function of the target protein or generates peptides that actively contribute to the death process. In the present study, we demonstrate that the cyclin-dependent kinase inhibitor p27Kip1 is cleaved by caspases in human leukemic cells exposed to apoptotic stimuli. We have shown recently that p27Kip1 overexpression delayed leukemic cell death in response to cytotoxic drugs. In transient transfection experiments, the p23 and the p15 N-terminal peptides generated by p27Kip1 proteolysis demonstrate an anti-apoptotic effect similar to that induced by the wild-type protein, whereas cleavage-resistant mutants have lost their protective effect. Moreover, stable transfection of a cleavage-resistant mutant of p27Kip1 sensitizes leukemic cells to drug-induced cell death. Altogether, these results indicate that proteolysis of p27Kip1 triggered by caspases mediates the anti-apoptotic activity of the protein.  (+info)

Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. (7/222)

Caspase-3 initiates apoptotic DNA fragmentation by proteolytically inactivating DFF45 (DNA fragmentation factor-45)/ICAD (inhibitor of caspase-activated DNase), which releases active DFF40/CAD (caspase-activated DNase), the inhibitor's associated endonuclease. Here, we examined whether other apoptotic proteinases initiated DNA fragmentation via DFF45/ICAD inactivation. In a cell-free assay, caspases-3, -6, -7, -8, and granzyme B initiated benzoyloxycarbonyl-Asp-Glu-Val-Asp (DEVD) cleaving caspase activity, DFF45/ICAD inactivation, and DNA fragmentation, but calpain and cathepsin D failed to initiate these events. Strikingly, only the DEVD cleaving caspases, caspase-3 and caspase-7, inactivated DFF45/ICAD and promoted DNA fragmentation in an in vitro DFF40/CAD assay, suggesting that granzyme B, caspase-6, and caspase-8 promote DFF45/ICAD inactivation and DNA fragmentation indirectly by activating caspase-3 and/or caspase-7. In vitro, however, caspase-3 inactivated DFF45/ICAD and promoted DNA fragmentation more effectively than caspase-7 and endogenous levels of caspase-7 failed to inactivate DFF45/ICAD in caspase-3 null MCF7 cells and extracts. Together, these data suggest that caspase-3 is the primary inactivator of DFF45/ICAD and therefore the primary activator of apoptotic DNA fragmentation.  (+info)

Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during apoptosis. (8/222)

Apoptosis is characterized by proteolysis of specific cellular proteins by a family of cystein proteases known as caspases. Gas2, a component of the microfilament system, is cleaved during apoptosis and the cleaved form specifically regulates microfilaments and cell shape changes. We now demonstrate that Gas2 is a substrate of caspase-3 but not of caspase-6. Proteolytic processing both in vitro and in vivo is dependent on aspartic residue 279. Gas2 cleavage was only partially impaired in apoptotic MCF-7 cells which lack caspase-3, thus indicating that different caspases can process Gas2 in vivo. In vitro Gas2 was processed, albeit with low affinity, by caspase-7 thus suggesting that this caspase could be responsible for the incomplete Gas2 processing observed in UV treated MCF-7 cells. In vivo proteolysis of Gas2 was detected at an early stage of the apoptotic process when the cells are still adherent on the substrate and it was coupled to the specific rearrangement of the microfilament characterizing cell death. Finally we also demonstrated that Gas2 in vitro binds to F-actin, but this interaction was unaffected by the caspase-3 dependent proteolytic processing.  (+info)

Neurodegenerative diseases pose one of the most pressing unmet medical needs today. It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently no disease-modifying therapies. Thus it is a potential target for neurodegenerative drug development. In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free structure shows caspase-6 in a partially mature but latent conformation. The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase ...
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Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of ...
Pain is a perceptive, unpleasant, multidimensional, sensory, emotional phenomenon that signals the possibility of physical harm. (Executioner) ...
48. Zavolan, M., Gerber, A.P. (2018) Mirroring the multifaceted role of RNA and its partners in gene expression. FEBS Lett. 592(17):2825-2827. doi: 10.1002/1873-3468.13230. 47. Albihlal, W.A., Gerber, A.P. (2018) Unconventional RNA-binding proteins: an uncharted zone in RNA biology. FEBS Lett. 592(17), 2917-2931. doi: 10.1002/1873-3468.13161. 46. Iadevaia, V. Matia-González, A.M, Gerber, A.P. (2018) An oligonucleotide-based tandem RNA isolation procedure to recover eukaryotic mRNA-protein complexes. J. Vis. Exp. 138. doi: 10.3791/58223. 45. King, H.A., El-Sharif, H.F., Matia-González, A.M., Iadevaia, V., Fowotade, A., Reddy, S.M., Gerber, A.P. (2017) Generation of ribosome imprinted polymers for sensitive detection of translational responses. Sci. Rep. 7(1), 6542. doi: 10.1038/s41598-017-06970-x. 44. Matia-González, A.M., Iadevaia, V., Gerber, A.P. (2017) A versatile tandem RNA isolation procedure to capture in vivo formed mRNA-protein complexes. Methods, 118-119, 93-100. (epub Oct 13, 2016. ...
India is preparing for its first executions in seven years, but the government could be forced to delay the hangings because of a lack of executioners.
TY - JOUR. T1 - Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury. AU - Singh, Amar B.. AU - Kaushal, Varsha. AU - Megyesi, Judit K.. AU - Shah, Sudhir V.. AU - Kaushal, Gur P.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Background. Caspase-6 is an important member of the executioner caspases in the caspase family of cell death proteases. The executioner caspases are the major active caspases detected in apoptotic cells and are generally considered to mediate the execution of apoptosis by cleaving and inactivating intracellular proteins. However, the complete characterization of mRNA and protein of caspase-6 in rat and its expression in normal kidney and in disease state has not been previously elucidated. Methods. A rat kidney cortex λgt10 cDNA library was screened to isolate the full-length caspase-6 cDNA. The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells. The expression in ...
Last month, federal Judge Beth Phillips said in a ruling in a death penalty case that it weighed heavily on her that condemned inmate Herbert Smulls had no legal means to learn more about how Missouris execution drug is made.. Under a Missouri law enacted in 2007, information that could be used to identify Missouri executioners is exempt from the states open records law. Under one of the laws provisions, executioners can sue anyone who knowingly releases their identities. When Missouri hired a compounding pharmacy last fall to produce drugs for its lethal injections, the Department of Corrections said it considered the pharmacy, as part of the execution team, to be secret under the law.. By the time Smulls case got to Phillips, the 8th Circuit U.S. Court of Appeals had already ruled that he was not entitled to learn more about the pharmacists making Missouris drugs for executions. The issue was moot, the court said, because Smulls had not proposed a more humane way to die. Phillips denied ...
Medieval style executioner. Full over-the-head latex mask. Individually hand painted for the most realistic look possible. (MC-TB26363)
ISTANBUL (AP) - Turkey's official news agency says three men suspected of carrying out murders on behalf of the Islamic State group were arrested.Anadolu...
On the morning of Jan. 8, 1908, the murderer John Boyd managed six hours of broken sleep in his Don Jail cell and, at around 7, newspaper readers lear...
4199-4207. The potential for best kratom strain to buy the use of cell proliferation and oncogene expression as intermediate markers during liver carcinogenesis. The p53-Mdm2 module and the ubiquitin system.. The fluorometric readings with SH-SY5Y cells which were treated with high doses Arena Ethnobotanicals Kratom Tincture ,iframe width="560″ height="315″ src="http://www.youtube.com/embed/to9joKDLAfM" frameborder="0″ allowfullscreen,. of MSE as early as 4 hr failed to show any significant caspase 8 and 9 activities. A second incubation time point at 18 hr also showed negative results. The next step was investigating the possibility of involvement of executioner caspases such as caspase 3 and 7.. These effects kratom vendors reviews are noticeable after 5 to 10 minutes and can last for several hours. Kratom contains a number of active components so-called alkaloids of which mitragynine is believed to be responsible for most of its effects. Mitragynine is an opioid agonist meaning that it ...
Studying brain disorders in people and developing drugs to treat them has been slowed by the inability to investigate single living cells from adult patients. In a first-of-its-kind study published in Cell Reports this week, a team from the Perelman School of Medicine at the University of Pennsylvania led by James Eberwine, PhD, a professor of Pharmacology, Sean Grady, MD, chair of Neurosurgery, and Junhyong Kim, PhD, a professor of Biology in Penns School of Arts & Sciences, was able to grow adult human neurons donated from patients ...
Inquiry (68726) for Abcams Recombinant mouse active Caspase-3 protein. Our in-house scientific support team are here to help you with any technical questions or queries
Purpose: To model the time evolution of active caspase-3 protein expression in a healthy lens, and in a lens exposed to UVR-300 nm (UVR-B). To develop an automated method to classify the fluorescent signal of biomarkers in the lens epithelial cells.. Methods: Six-week old Sprague-Dawley rats were used. Firstly, expression of active caspase-3 was studied in the lens epithelium of healthy rats. Secondly, rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-B for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR-B exposure, the exposed and the contralateral non-exposed lenses were removed. Immunohistochemistry was done on three mid-sagittal sections from each lens. The florescent labelling for active caspase-3 in each lens section was counted three times. The time evolution of active caspase-3 expression in response to UVR-B exposure was modelled as a function of cell position in the lens epithelium. An automated objective method was developed to quantify the lens epithelial cells and to ...
The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis.: Acco
Chavoret Jaruboons memoirs in English and Thai Up until 1934, the official method of execution in Thailand was by decapitating (see The Last Public Be...
Police investigating the murder of newlywed Catherine Mullany are probing possible links between her killing and a recent execution-style shooting in Antigua.
I am the wound and the knife! I am the slap and the cheek! I am the limbs and the rack, And the victim and the executioner! I am the vampire of my own heart. ~ Charles Baudelaire.
zVAD-fmk does not totally abrogate FasL-triggered apoptosis in HeLa cells expressing caspase-10 at low level.A, B, Casp10+ and Casp10- HeLa cells were incubated
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Outrageous indeed. I couldnt agree more with IPA director-general Hamish Pringles take on Thomas Cookes contribution to an increasingly acrimonious global media-buying debate. The travel operator is reported to be demanding a £1m signing-on fee at the conclusion of its £30m media review - in addition to a reduction in agency fees currently paid and…
TY - JOUR. T1 - Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. AU - Mazroui, Rachid. AU - Di Marco, Sergio. AU - Clair, Eveline. AU - Von Roretz, Christopher. AU - Tenenbaum, Scott A.. AU - Keene, Jack D.. AU - Saleh, Maya. AU - Gallouzi, Imed Eddine. PY - 2008/1/14. Y1 - 2008/1/14. N2 - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is ...
Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...
Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid β (Aβ) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (ΔTau) by executioner caspases. Following caspase-cleavage, ΔTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. ΔTau can be phosphorylated by glycogen synthase kinase-3β and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, ΔTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, ΔTau colocalizes with Aβ1-42 and is induced by Aβ1-42 in vitro. Collectively, our data ...
The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. had not been detectable in neutrophils isolated from VX-950 dynamic plaques. Significant medical reactions to secukinumab had been noticed 2?weeks following a solitary infusion, connected with extensive clearance of cutaneous neutrophils parallel towards the normalization of keratinocyte abnormalities and reduced amount of IL-17-inducible neutrophil chemoattractants (e.g. (TNF-(monoclonal antibody selective for IL-17A, or placebo inside a 3:3:3:1 percentage (information regarding test size computation, randomization and blinding are given within the Assisting Information). There have been low- and middle- single-dose cohorts who received secukinumab 3 and 10?mg/kg, respectively, infused on Day time 1 (with placebo administered on Day time 15 and Day time 29) along with a high-dose cohort who have received 3 infusions of secukinumab ...
Only days after U.S. President Donald J. Trump spoke about the situation in Sweden, a live hand grenade was found in a park in the city. Police say they were looking for a weapon in connection with a shooting in the same area but dont believe the grenade had anything to do with the shooting leading to speculation from many of what the object was doing there ...
First, the up to date Ensembl IDs have been retrieved for the many genes with SD three between rapamycin and Ly294002 therapies. The Amuvatinib 溶解度 GO lessons
As one of the Imperiums many staging grounds for the forces serving in the Great Crusade, the verdant world of Tallarn has long served as a transfer point for vast numbers of military personnel and their war machines. Now, destroyed by a deadly virus-bomb attack launched by the battered Iron Warriors fleet, the entire world is reduced to a toxic wasteland where the survivors must fight to defend what little remains of their home. The remnants of the once-mighty Jurnian 701st armoured regiment emerge from their underground shelters, and the opening movements of the Battle of Tallarn begin...[1] ...
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Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
Effects of ponicidin on the activity of caspase-3 in MKN28 cells. After treatment, the activity of caspase-3 in MKN28 cells was analyzed by the caspase-3 assay
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Epidemiological studies indicate that components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. In the present study, we investigated the effect of newly isolated phenylamine derivative N-benzyl-N-methyldecan-1-amine (NBNMA) from garlic cloves on the inhibition of the growth and apoptosis of human leukemia U937 cells and its potential anticancer mechanism. NBNMA exhibited an antiproliferative effect in U937 cells by inducing cell cycle arrest at the G2/M phase and apoptotic cell death. Western blot analyses revealed that NBNMA decreased the expression of the regulator genes of G2/M phase progression, cyclin dependent kinase (Cdk) 2 and Cdc2 and elevated the expression of the Cdk inhibitor p21WAF1/CIP1 in a p53-independent manner. In addition, NBNMA activated caspase-8 and caspase-9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis, respectively, which led to activation of executioner caspase-3 along with degradation of ...
INTRODUCTION Scientists are building detailed maps of the cellular composition in the human brain to learn about its development. In the human cortex, the largest area of the mammalian brain, neural circuits are formed through anatomical refinement, including axon and synaptic pruning, and the emergence of complex patterns of network activity during early fetal development. Cellular analyses in the human brain are restricted to postmortem material, which cannot reveal the process of development. Model organisms are, therefore, commonly used for studies of brain physiology, development, and pathogenesis, but the results from model organisms do not always translate to humans. RATIONALE Systems to model human neuron dynamics and their dysfunction in vivo are needed. While biopsy specimens and the generation of neurons from induced pluripotent stem cells (iPSCs) could provide the necessary human genetic background, two- and three-dimensional cultures lack factors that normally support neuronal ...
Free Online Library: Samaritan Discovers Long-Sought-After Small Molecule Drug That Induces Human Neuron Differentiation. by Business Wire; Business, international
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What I understand from my colleagues, since I dont supervise intelligence agencies, [is] that there were organisations which helped illegal migrants to find ways to Hungary, to find where they could violate our border, to find out how to apply for asylum status, and these reports have said that George Soros was in the background for these organisations," he said ...
Rabbit polyclonal active Caspase-3 antibody validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 2 publications and 3 independent…
Complete information for CASP5 gene (Protein Coding), Caspase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Caspase 6 in turn activates HIPK2. Conversly, p53 down regulates HIPK2 by activating the ubiquitin ligase mdm2. An interaction ... MacLachlan TK, El-Deiry WS (July 2002). "Apoptotic threshold is lowered by p53 transactivation of caspase-6". Proceedings of ... p53 binds to the third intron of the caspase 6 gene, and promotes the activation of the gene. ... Caspase 6 cleaves HIPK2 at residue D916 and D977. As a result, the auto-inhibitory domain is removed and the activity of HIPK2 ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... M (y) 5, 6, 7 ; H (ny) D (y) 11 M (y) 14; R (y) 15; D (y) 16, 18; H (ny) ... 106 (6): 2364-74. Bibcode:2006JNeur..26.9606G. doi:10.1111/j.1471-4159.2008.05578.x. PMID 18643871.. ... 14 (6): 488-92. Bibcode:1996CBio....6.1213A. doi:10.1016/j.cub.2004.03.003. PMID 15043813.. ...
2004). "Regulation of caspase-6 and FLIP by the AMPK family member ARK5". Oncogene. 23 (42): 7067-75. doi:10.1038/sj.onc. ... "ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but ...
It is also involved in an apoptotic pathway characterized by activation of caspase-6. THOC7 is also part of the same subcomplex ... Scientific reports, 6, 19413. Xu, X. Q., Soo, S. Y., Sun, W., & Zweigerdt, R. (2009). Global expression profile of highly ... The gene contains 12 distinct introns, 11 exons, produces 7 different mRNAs, and 6 alternatively spliced variants. The promotor ...
Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. „Blood ... Environ Health Perspect". 91, s. 165-6, Feb 1991. PMID: 2040245. *↑ a b c d B. Deschler, M. Lübbert. Acute myeloid leukemia: ... Blood". 98 (6), s. 1714-20, Sep 2001. PMID: 11535502. *↑ T. Mercher, GD. Raffel, SA. Moore, MG. Cornejo i inni. The OTT-MAL ... Blood". 98 (6), s. 1752-9, Sep 2001. PMID: 11535508. *↑ C. Thiede, C. Steudel, B. Mohr, M. Schaich i inni. Analysis of FLT3- ...
The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase-7, thereby inhibiting their activation and ... By inhibiting caspase 8, crmA prevents the other caspases from ever being activated. Inhibition of caspase 8 also prevents cell ... Caspase 8 initiates apoptosis by activating "executioner" caspases, numbered 3, 6, and 7. ... Bcl-2 Caspase cIAP1 cIAP2 Inhibitor of apoptosis domain Survivin XIAP Schwerk C, Schulze-Osthoff K (July 2005). "Regulation of ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
2007). "Cells with defective p53-p21-pRb pathway are susceptible to apoptosis induced by p84N5 via caspase-6". Cancer Res. 67 ( ...
Caspase recruitment domain-containing protein 10 is an enzyme that in humans is encoded by the CARD10 gene. The caspase ... "Entrez Gene: CARD10 caspase recruitment domain family, member 10". Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S ... "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and ... Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J (June 2001). "Card10 is a novel caspase recruitment domain/membrane- ...
Galande S, Dickinson LA, Mian IS, Sikorska M, Kohwi-Shigematsu T (Aug 2001). "SATB1 cleavage by caspase 6 disrupts PDZ domain- ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (Oct ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T (Aug 1992). "A ... 280 (6): 5004-12. doi:10.1074/jbc.M411718200. PMID 15561718. Wen J, Huang S, Rogers H, Dickinson LA, Kohwi-Shigematsu T, ...
p.S30-S38 Graham, RK; Deng, Y; Slow, EJ; et al.Cleavage at the caspase-6 site is required for neuronal dysfunction and ... Surprisingly, both necrotic and apoptotic processes utilize a similar intracellular signaling cascade which uses caspase ... and Morphine-6-Glucuronide-induced Respiratory Depression in Healthy Volunteers: A Mechanism-based Pharmacokinetic- ...
... 不同於一般細胞凋亡的機制需要激發caspase-3蛋白,神經軸突的退化需要激發caspase-6蛋白,而且是在神經軸突上呈現點狀散佈的激發,進而造成軸突的凋亡。此外,經由caspase-6路徑所啟動的細胞凋亡,也可能和另一種神經退化疾病-杭廷頓舞蹈症相關 ... Cleavage at the caspase-6 site is required for neuronal
2000). "Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during ... The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes ... 74 (6): 1255-61. doi:10.1086/421527. PMC 1182089 . PMID 15124103. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status ... 117 (6): 1251-61. doi:10.1083/jcb.117.6.1251. PMC 2289493 . PMID 1607387. Schneider C, King RM, Philipson L (1988). "Genes ...
2002). "The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during ... doi:10.1016/S0006-291X(02)02834-6. PMID 12504083. Krona C, Ejeskär K, Abel F, et al. (2003). "Screening for gene mutations in a ...
2002). "The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during ...
It also selectively inhibits effector caspases 2, 3, 6, and 7 but not caspases 8 and 10. This compound has been shown to block ...
P35 has been shown to be a caspase inhibitor with a very wide spectrum of activity both in regard to inhibited caspase types ... However, unlike other caspase substrate proteins, the fragments of P35 do not dissociate from the caspase after cleavage. ... "Mutational analyses of the p35-caspase interaction. A bowstring kinetic model of caspase inhibition by p35". Journal of ... The mechanism of caspase inhibition was discovered by Guozhou Xu in the team of Hao Wu at the Department of Biochemistry at ...
Alcivar A, Hu S, Tang J, Yang X (Jan 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2 ... Alcivar A, Hu S, Tang J, Yang X (2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2): ... Schickling O, Stegh AH, Byrd J, Peter ME (2002). "Nuclear localization of DEDD leads to caspase-6 activation through its death ... DEDD has been shown to interact with: CFLAR, Caspase 8, and FADD. GRCh38: Ensembl release 89: ENSG00000158796 - Ensembl, May ...
Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ... "Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ...
"Transcription factor AP-2alpha is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor ... 21 (6): 665-76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft ... 272 (23): 14611-6. doi:10.1074/jbc.272.23.14611. PMID 9169421. Batsché E, Muchardt C, Behrens J, Hurst HC, Crémisi C (Jul 1998 ... 50 (6): 847-61. doi:10.1016/0092-8674(87)90512-5. PMID 3040262. Williams T, Admon A, Lüscher B, Tjian R (Dec 1988). "Cloning ...
This trial will test the use of a synthetic siRNA that blocks caspase 2, an important enzyme in the apoptosis cycle. In ... "Ocular neuroprotection by siRNA targeting caspase-2". Cell Death & Disease. 2 (6): e173. doi:10.1038/cddis.2011.54. PMC 3168996 ... In approximately 6 months following the infarct visual acuity improves by 3 or more lines of vision on the Snellen Chart (the ... showed that visual acuity can improve up to 6 months and not after that. To minimize the risk of further visual loss in the ...
Chen, Y R; Kori R; John B; Tan T H (Nov 2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... Chen YR, Kori R, John B, Tan TH (2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... HCLS1 has been shown to interact with Caspase 3. GRCh38: Ensembl release 89: ENSG00000180353 - Ensembl, May 2017 GRCm38: ... induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells". ...
"Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 ...
... which resembles that of the animal caspases. Similarly to the animal caspases, the phytaspase is a cell death promoting ... In contrast with the animal caspases, that exist in the cytoplasm in a form of pre-synthesized precursors, the activation of ... Porter, A. G.; Jänicke, R. U. (1999-02-01). "Emerging roles of caspase-3 in apoptosis". Cell Death and Differentiation. 6 (2): ... The phytaspase displays a strict substrate specificity, which resembles that of the animal caspase-3. It recognizes a ...
Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity". Cell Death and Differentiation. 9 (1): 20-6. ... reducing the cell's inhibition to caspase activation. In summary, HTRA2/Omi contributes to apoptosis through both caspase- ... Suzuki Y, Takahashi-Niki K, Akagi T, Hashikawa T, Takahashi R (Feb 2004). "Mitochondrial protease Omi/HtrA2 enhances caspase ... caspase-independent, necrosis-like programmed cell death mediated by serine protease activity". Blood. 103 (6): 2299-307. doi: ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 460 (7255): 632-6. Bibcode:2009Natur.460..632Z. doi:10.1038/nature08177. PMC 2744588. PMID 19641596.. ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation ... Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals ... Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 ...
... Jun 17, 2006, 20:10, Reviewed by: Dr. Himanshu Tyagi. ... In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. By blocking the action ... In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. By blocking the action ...
Rabbit polyclonal active Caspase-6 antibody. Validated in WB and tested in Mouse, Rat, Human. Cited in 1 publication(s). ... The caspase family of cysteine proteases has been shown to play a key role in apoptosis. Similar to other caspases, caspase 6 ... The caspase family of cysteine proteases has been shown to play a key role in apoptosis. Similar to other caspases, caspase 6 ... Together with caspase 3, caspase 6 is one of the major caspases in apoptotic cells, and functions downstream of apoptosis ...
Rabbit polyclonal Caspase-6 / CASP-6 antibody validated for WB, IHC and tested in Human. Immunogen corresponding to recombinant ... Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits. ... Anti-Caspase-6 / CASP-6 antibody (ab155241) at 1/500 dilution + Jurkat whole cell lysate at 30 µg. Predicted band size: 33 kDa ... Anti-Caspase-6 / CASP-6 antibody. See all Caspase-6 / CASP-6 primary antibodies. ...
From: The prodomain of caspase-3 regulates its own removal and caspase activation ... b A caspase-3 activity assay was used to determine the ability to cleave a DEVD-chromphore substrate. c Cell death was ... d Cells were serum starved for 24 h and the cleavage pattern of caspase-3 was determined using western blot analysis. Actin was ... C3 D9E is inefficiently cleaved resulting in decreased caspase activation and cell death. , Cell Death Discovery ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
Caspase-6 (Cysteine-Requiring Aspartate Proteases) is part of a family of intracellular cysteine proteases that cleave their ... Caspase-3, caspase-8 and caspase-10 can cleave procaspase-6. Active caspase-6 cleaves several other proteins such as lamins, ... Together with caspases-3 and -7, the isoform of caspase-6 is classified as an effector/execution caspase. ... Recombinant catalytically active caspase-6was western blotted with Active/Cleaved Caspase-6 antibody. Theantibody detected both ...
Caspases are a family of cysteine proteases which are the major executors of apoptosis and inflammation. Caspases can be ... Firstly, compared with those of initiator caspases, the pro-domains of effector caspases are short (23-28 residues in length) ... However, in contrast to the above scheme, CASP6 is often activated by CASP3 rather than initiator caspases (Slee et al., 1999. ... In addition, caspases prefer a small and uncharged residue after the P1 aspartate (also known as P1′; Timmer & Salvesen, 2007. ...
Caspase 6 antibody for Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)). ... Apoptosis, Caspase Cascade in Apoptosis Application Details Product Details anti-Caspase 6 Antibody Target Details Caspase 6 ... Recommended Caspase 6 Antibody (supplied by: Log in to see ) Antigen Caspase 6, Apoptosis-Related Cysteine Peptidase (CASP6) ... This Caspase 6 antibody is un-conjugated Alternatives Biotin. (18), FITC. (17), HRP. (13), APC. (10), Alkaline Phosphatase (AP) ...
... as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60). These caspases are responsible for the proteolysis of the majo ... as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60). These caspases are responsible for the proteolysis of the ... Caspase-6 can cleave its prodomain to produce mature caspase-6, which directly activates caspase-8 (EC 3.4.22.61) and leads to ...
As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free ... The crystal structure of caspase-6, a selective effector of axonal degeneration. Renato Baumgartner, Gabriele Meder, Christophe ... It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently ... The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. ...
Detect caspase-6 activation in vitro with the FAM FLICA Caspase 6 Assay Kit to investigate apoptosis and pyroptosis in whole ... FAM-FLICA® Caspase-6 Assay Kit. $195.00 - $561.00. Detect caspase-6 activity with the FLICA Caspase-6 Assay Kit. This in vitro ... FLICA Caspase-6 Reagent (FAM-VEID-FMK), 1 vial, #654. • 10X Apoptosis Wash Buffer, 15 mL, #635. • Fixative, 6 mL, #636. • ... FLICA Caspase-6 Reagent (FAM-VEID-FMK), 4 vials, #654. • 10X Apoptosis Wash Buffer, 60 mL, #634. • Fixative, 6 mL, #636. • ...
Induction of caspase-3 cleavage in human HuH7 cells at 2.5 to 5 uM incubated for 6 to 24 hrs by Western blot. ...
Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC... ... Check for Discount on Caspase 6 (Apoptotic Protease Mch 2 or ... Small Molecules to Inhibit Caspase 3 and Caspase 6 for Huntingtons Disease - Drug Profile 33. Product Description 33. ... Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) - Pipeline Review, H2 2016. Summary. Global Markets Directs, ... The report assesses Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) targeted therapeutics based on mechanism of ...
... and JNK may be an upstream effector of caspase activation. This article has been cited by other articles: Z. Chen, L. W. Forman ... The Recruitment of Fas-associated Death Domain/Caspase-8 in Ras-induced Apoptosis1 Chang-Yan Chen2, Peter Juo, James S. Liou, ... Suppression of JNK by dn-JNK1 blocked the interaction of FADD and caspase-8 and partially protected Jurkat/ras and Jurkat/Fasm/ ... During this Ras-induced apoptotic process, caspase-8 was activated, possibly through its binding to Fas-associated death domain ...
... which leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3; caspase-9 thus is the most ... Feedback cleavage of caspase-9 by caspase-3 again significantly increases the activity of the apoptosome . Caspase-9 plays a ... 7 are targets of caspase-9 activity . Caspase-9 forms dimers in the course of activation. Cytochrome c/Apaf-1/caspase-9 form a ... Apart from cleavage of caspase-3, the downstream enzymes caspase-6 and - ...
Loegering, D. A. ; Ruchaud, S. ; Earnshaw, W. C. ; Kaufmann, Scott H. / Evaluation of the role of caspase-6 in anticancer drug- ... Loegering, D. A., Ruchaud, S., Earnshaw, W. C., & Kaufmann, S. H. (2006). Evaluation of the role of caspase-6 in anticancer ... Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis [1]. / Loegering, D. A.; Ruchaud, S.; Earnshaw, W. C. ... Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis [1]. Cell Death and Differentiation. 2006 Feb 1;13(2): ...
Caspase_6 Colorimetric Assay Kit \ K115-100 for more molecular products just contact us ... Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. The Caspase-6 Colorimetric Assay Kit ... Index / Biovis / Caspase_6 Colorimetric Assay Kit / Product Detail : K115-100 Caspase_6 Colorimetric Assay Kit. Related ... We have also other products like : Caspase_6 Colorimetric Assay Kit. Related products : Caspase_6 Colorimetric Assay Kit ...
Caspase-6 Inhibitor Z-VEID-FMK \ 1011-20C for more molecular products just contact us ... 11953316] Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation.. ... 24363090] A synergic role of caspase-6 and caspase-3 in Tau truncation at D421 induced by H2O 2.. [22259050] Honokiol traverses ... We recommend using 1000-5000X dilutions for inhibiting caspase-6 activity in Jurkat cell culture (e.g., Add 1 μl to 1-5 ml of ...
Caspase_6 Colorimetric Assay Kit25 assays \ K115-25 for more molecular products just contact us ... Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. The Caspase-6 Colorimetric Assay Kit ... 10638661] Caspases -2, -3, -6, and -9, but not caspase-1, are activated in sepsis-induced thymocyte apoptosis.. ... We have also other products like : Caspase_6 Colorimetric Assay Kit25 assays. Related products : Caspase_6 Colorimetric Assay ...
Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant ... The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8- ... Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. ... caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. ...
MCH2; Caspase-6; CASP-6; Apoptotic protease Mch-2; CASP6. Background. Involved in the activation cascade of caspases ...
Functional proteomics of resveratrol-induced colon cancer cell apoptosis: Caspase-6-mediated cleavage of lamin A is a major ... Caspase-6-mediated cleavage of lamin A is a major signaling loop. Proteomics 6 (8) : 2386-2394. [email protected] Repository. ...
Caspase_6 (Active) Antibody \ 3156-100 for more molecular products just contact us ... Similar to other caspases, caspase-6 is also synthesized as an inactive pro-enzyme that is processed in cells undergoing ... Together with caspase-3, caspase-6 is one of the major caspases in apoptotic cells, and functions downstream of apoptosis ... Caspase_6 (Active) Antibody antibody storage GENTAUR recommends for long therm storage to freeze at -24 C. For short time ...
Caspase_6 P Antibody \ 3256-100 for more molecular products just contact us ... Similar as other caspases, caspase-6 is also synthesized as an inactive pro-enzyme that is processed in cells undergoing ... Caspase_6 P Antibody antibody storage GENTAUR recommends for long therm storage to freeze at -24 C. For short time storage up ... Caspase-6 has also been shown involving in the proteolysis of poly (ADP-ribose) polymerase (PARP) and nuclear lamin A. ...
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
  • Moreover, the biochemical form of caspase-8 differed in the two pathways. (wikipedia.org)
  • In a recent work aimed to identify the presence of alternative small RNA pathways which could contribute to the posttranscriptional control in T. cruzi , we reported the presence of homogeneous population of small RNAs derived from mature tRNAs representing from 25 to 30% of the small RNA population [ 6 ]. (hindawi.com)
  • But more recent works [ 6 , 7 , 13 ] pointing to the ability of highly diluted (dynamized) drugs showing positive effects on the face of their physical non-existence have reopened the search for other possible molecular pathways of activities. (hindawi.com)
  • In summary, HTRA2/Omi contributes to apoptosis through both caspase-dependent and -independent pathways. (wikipedia.org)
  • Its IUPAC name is (3R,4S)-4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6-oxo-3H-2-benzopyran-7-carboxylic acid and the molecular formula is C13H14O5. (wikipedia.org)
  • Synthetic peptide surrounding amino acids mapping to the C-terminus of the large fragment of Human Caspase-6. (abcam.com)
  • The resulting IgG fraction is further purified by absorption on the Caspase-3 peptide (Human, amino acids 167-178) corresponding to the uncleaved Caspase 3 site sequence. (abcam.com)
  • Within caspase-9's active site, in order for catalytic activity to occur there has to be specific amino acids in the right position. (wikipedia.org)