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.
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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
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.
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.
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.
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.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
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.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
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.
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.
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 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.
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)
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A 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)
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.
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.
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.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
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.
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.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
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.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
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.
Peptides composed of between two and twelve amino acids.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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 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.
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.
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)
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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)
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.
Physiologically inactive substances that can be converted to active enzymes.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
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.
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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.
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.
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.
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.
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.
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.
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.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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).
Proteins prepared by recombinant DNA technology.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A 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.
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.
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.
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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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 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.
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.
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.
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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
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.
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.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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).
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)
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.
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.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A 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).
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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).
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.
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.
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.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
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.
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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
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.
Compounds that inhibit cell production of DNA or RNA.
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.
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.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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.
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.
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.
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.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
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)
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
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.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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 proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A 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.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
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.
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)
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.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
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.
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.
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.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
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.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
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.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
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)
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.
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.
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.
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.)
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.
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.
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)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

Identification of a new caspase homologue: caspase-14. (1/27)

Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis. Here, we report the identification of a new murine caspase homologue, viz. caspase-14. It is most related to human/murine caspase-2 and human caspase-9, possesses all the typical amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain. Murine caspase-14 shows 83% similarity to human caspase-14. Human caspase-14 is assigned to chromosome 19p13.1. Northern blot analysis revealed that mRNA expression of caspase-14 is undetectable in all mouse adult tissues examined except for skin, while it is abundantly expressed in mouse embryos. In contrast to many other caspase family members, murine caspase-14 is not cleaved by granzyme B, caspase-1, caspase-2, caspase-3, caspase-6, caspase-7 or caspase-11, but is weakly processed into p18 and p11 subunits by murine caspase-8. No aspartase activity of murine caspase-14 could be generated by bacterial or yeast expression. Transient overexpression of murine caspase-14 in mammalian cells did not elicit cell death and did not interfere with caspase-8-induced apoptosis. In conclusion, caspase-14 is a member of the caspase family but no proteolytic or biological activities have been identified so far. The high constitutive expression levels in embryos and specific expression in adult skin suggest a role in ontogenesis and skin physiology.  (+info)

Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. (2/27)

Programmed cell death of epidermal keratinocytes (KC) results in the formation of cornified cells, which constitute the outermost skin layer, the stratum corneum. Here we show by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry that epidermal KC express caspase-14, a member of the caspase family of pro-apoptotic proteases, in a tissue-specific manner. Caspase-14 protein abundance strongly increases during terminal differentiation of KC in vivo and in vitro. Under conditions that lead to stratum corneum formation caspase-14 cleavage products, which indicate proenzyme activation, appeared in the KC lysates. Cleavage of the enzyme was also detected in lysates from normal human epidermis and in extracts of stratum corneum. Our findings demonstrate that caspase-14 is activated during KC differentiation and strongly suggest that it is involved in the formation of the human skin barrier.J Invest Dermatol 115:1148-1151 2000  (+info)

Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing. (3/27)

The epidermis is a stratified squamous epithelium in which keratinocytes progressively undergo terminal differentiation towards the skin surface leading to programmed cell death. In this respect we studied the role of caspases. Here, we show that caspase-14 synthesis in the skin is restricted to differentiating keratinocytes and that caspase-14 processing is associated with terminal epidermal differentiation. The pro-apoptotic executioner caspases-3, -6, and -7 are not activated during epidermal differentiation. Caspase-14 does not participate in apoptotic pathways elicited by treatment of differentiated keratinocytes with various death-inducing stimuli, in contrast to caspase-3. In addition, we show that non-cornifying oral keratinocyte epithelium does not express caspase-14 and that the parakeratotic regions of psoriatic skin lesions contain very low levels of caspase-14 as compared to normal stratum corneum. These observations strongly suggest that caspase-14 is involved in the keratinocyte terminal differentiation program leading to normal skin cornification, while the executioner caspases are not implicated. Cell Death and Differentiation (2000) 7, 1218 - 1224  (+info)

Expression and transcriptional regulation of caspase-14 in simple and complex epithelia. (4/27)

Caspase-14 is a recent addition to the caspase family of aspartate proteases involved in apoptotic processes. Human caspase-14 appears to be only weakly processed during apoptosis, and it does not cleave classical caspase substrates. Post partum, caspase-14 is prominently expressed by human keratinocytes and reportedly participates in terminal differentiation of complex epithelia. Here we provide evidence challenging the view that caspase-14 expression or processing is linked exclusively to terminal keratinocyte differentiation. We demonstrate that caspase-14 expression extended to multiple cell lines derived from simple epithelia of the breast, prostate, and stomach. In keratinocytes and breast epithelial cells, caspase-14 expression was upregulated in high-density cultures and during forced suspension culture. These effects were primarily due to transcriptional activation as indicated by reporter gene assays using a 2 kb caspase-14 promoter fragment. Importantly, caspase-14 was not cleaved during forced suspension culture of either cell type although this treatment induced caspase-dependent apoptosis (anoikis). Forced expression of caspase-14 in immortalized human keratinocytes had no effect on cell death in forced suspension nor was the transfected caspase-14 processed in this setting. In contrast to postconfluent and forced suspension culture, terminal differentiation of keratinocytes induced in vitro by Ca2+ treatment was not associated with increased caspase-14 expression or promoter activity. Our results indicate that (1) caspase-14 is expressed not only in complex but also simple epithelia; (2) cells derived from complex and simple epithelia upregulate caspase-14 expression in conditions of high cell density or lack of matrix interaction and; (3) in both cell types this phenomenon is due to transcriptional regulation.  (+info)

Caspase-14 expression by epidermal keratinocytes is regulated by retinoids in a differentiation-associated manner. (5/27)

Caspase-14 is the only member of the caspase family that shows a restricted tissue expression. It is mainly confined to epidermal keratinocytes and in contrast to other caspases, is not activated during apoptosis induced by ultraviolet irradiation or cytotoxic substances. As it is cleaved under conditions leading to terminal differentiation of keratinocytes we suggested that caspase-14 plays a part in the physiologic cell death of keratinocytes leading to skin barrier formation. Here we show that retinoic acid, at concentrations inhibiting terminal differentiation of keratinocytes, strongly suppressed caspase-14 mRNA and protein expression by keratinocytes in monolayer culture and in a three-dimensional in vitro model of differentiating human epidermis (skin equivalent). By contrast, the expression of the caspases 3 and 8, which are both activated during conventional apoptosis, was increased and unchanged, respectively, after retinoic acid treatment. In addition to inhibition of differentiation in skin equivalents, retinoic acid treatment led to keratinocyte apoptosis and activation of caspase-3, both of which were undetectable in differentiated control skin equivalents. As this occurred in the absence of detectable caspase-14, our data demonstrate that caspase-14 is dispensable for keratinocyte apoptosis. The fact that in contrast to caspase-3 and caspase-8, caspase-14, similarly to other keratinocyte differentiation-associated proteins, is downregulated by retinoids, strongly suggests that this caspase, but not caspase-3 and -8, plays a part in terminal keratinocyte differentiation and skin barrier formation.  (+info)

Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin cultures. (6/27)

Caspase-14 is a nonapoptotic caspase family member whose expression in the epidermis is confined to the suprabasal layers, which consist of differentiating keratinocytes. Proteolytic activation of this caspase is observed in the later stages of epidermal differentiation. In psoriatic skin, a dramatic decrease in caspase-14 expression in the parakeratotic plugs was observed. Topical treatment of psoriatic lesions with a vitamin D3 analogue resulted in a decrease of the psoriatic phenotype and an increase in caspase-14 expression in the parakeratotic plugs. To investigate whether vitamin D3 directly affects caspase-14 expression levels, we used keratinocyte cell cultures. 1alpha,25-Dihydroxycholecalciferol, the biologically active form of vitamin D3, increased caspase-14 expression, whereas retinoic acid inhibited it. Moreover, retinoic acid repressed the vitamin D3-induced caspase-14 expression level. In addition, the use of organotypic skin cultures demonstrated that 1alpha,25-dihydroxycholecalciferol enhanced epidermal differentiation and caspase-14 activation, whereas retinoic acid completely blocked caspase-14 processing. Our data indicate that caspase-14 plays an important role in terminal epidermal differentiation, and its absence may contribute to the psoriatic phenotype.  (+info)

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14. (7/27)

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.  (+info)

Stratum corneum-derived caspase-14 is catalytically active. (8/27)

Caspase-14, a cysteine protease with restricted tissue distribution, is highly expressed in differentiated epidermal keratinocytes. Here, we extracted soluble proteins from stratum corneum (SC) of human epidermis and demonstrate that the extract cleaves tetrapeptide caspase substrates. The activity decreased to below 10% when caspase-14 was removed by immunodepletion showing that caspase-14 is the predominant caspase in SC. In contrast to normal SC, where caspase-14 was present exclusively in its processed form, incompletely matured SC of parakeratotic skin from psoriasis and seborrheic dermatitis contained both procaspase-14 and caspase-14 subunits. Fractionation of extract from parakeratotic SC revealed that the peak caspase activity coeluted with processed caspase-14 but not with procaspase-14. Our results suggest that during regular terminal keratinocyte differentiation, endogenous procaspase-14 is converted to caspase-14 subunits that are catalytically active in the outermost layers of normal human skin.  (+info)

Mouse anti Human caspase-14, clone 4C9 recognizes human caspase-14, a 242 amino acid ~28 kDa non-apoptotic caspase which exists as a
Looking for online definition of cornification in the Medical Dictionary? cornification explanation free. What is cornification? Meaning of cornification medical term. What does cornification mean?
BioAssay record AID 513048 submitted by ChEMBL: Inhibition of human caspase-3-mediated apoptosis assessed as Ac-DEVD-7-amino-4-methylcoumarin cleavage product at 100 uM by fluorescence assay.
|p|Although the precise biological role of lysosomal membrane-associated glycoproteins (LAMPs) and ABH histo-blood group antigens (HBGAs) remains somewhat unclear, they are thought to be related to cell differentiation, cellular adhesion, and tumorigenesis. Here, we present the first comparative immunohistochemical study of both LAMPs and HBGAs in normal and neoplastic skin. Their localization is compared to that of high molecular weight cytokeratin and cytokeratin MNF 116. LAMPs and HBGA were differentially expressed in the normal stratified squamous epithelium, suggesting that they are involved in the initial steps of the differentiation process, whereas HBGAs are characteristic of terminal keratinocyte differentiation. No change in the reactivity for HBGA was detected in the stratified epithelium overlying squamous cell or basal cell carcinomas, whereas a considerable loss of LAMPs was detected. LAMPs were overexpressed in tumor cells, whereas HBGAs were lost in tumor zones of
Define filaggrin. filaggrin synonyms, filaggrin pronunciation, filaggrin translation, English dictionary definition of filaggrin. n a protein found in skin cells Noun 1. filaggrin - the main protein of the keratohyalin granules; the specific target of the immune response in rheumatoid...
(a) Nuclear suprabasal beta-catenin (β-catenin) staining expression in all layers of epidermis except the parakeratotic and cornified layers of a psoriasis les
Kit Component:- KN219792G1, FLG gRNA vector 1 in pCas-Guide vector- KN219792G2, FLG gRNA vector 2 in pCas-Guide vector- KN219792D, donor vector…
Filaggrin is a structural protein in the stratum corneum (SC) that is produced as the ~500-kDa precursor protein profilaggrin. Profilaggrin is the major component of keratohyalin granules within the granular layer. Individual filaggrin monomers are released proteolytically during epidermal differentiation, and they contribute to macrofibril generation and the mechanical strength and integrity of the SC. Filaggrin monomers are finally degraded into natural moisturizing factors, which are believed to maintain hydration of the upper SC.Mutations in the filaggrin gene were reported to cause ichthyosis vulgaris [1] and were also identified as a major predisposing factor for atopic dermatitis (AD) [2]. Disruption of the SC barrier caused by filaggrin deficiency may lead to percutaneous allergenic sensitization, a primary event in the pathogenesis of AD [3, 4]. Although various reports have suggested a role for filaggrin in SC barrier formation, the absence of mice specifically lacking filaggrin has ...
BACKGROUND: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. METHODS: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. ...
The differentiation of keratinocytes involves numerous steps including the formation of the cornified envelope and the aggregation of keratin filaments by filaggrin monomer molecules. In this study, we investigated whether mu-calpain is involved in the processing of profilaggrin to filaggrin monomer …
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Disorder of Cornification 12 (Neutral Lipid Storage Type) information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
Gentaur molecular products has all kinds of products like :search , Neuromi \ Filaggrin, monoclonal antibody, mouse, 100 ul. \ MO20041-100 for more molecular products just contact us
Patients with by systemic rheumatic diseases (SRDs) are at significantly greater risk of cardiovascular (CV) risk factors, CV events, and mortality than the general population. Although CV involvement in such patients is highly heterogeneous and may affect various structures of the heart, it can now be diagnosed earlier and promptly treated.The examinations used include transthoracic or transesophageal echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) to investigate valve abnormalities, pericardial disease and ventricular wall motion defects. Coronary arteries can be investigated invasively using quantitative coronarography or intravascular ultrasound (IVUS) to assess coronary diameter, or non-invasively using transthoracic or transesophageal ultrasonography (US), MRI, positron emission tomography (PET) after endothelium-dependent vasodilatory provocation, or CT to assess coronary flow reserve. Finally, peripheral circulation can be measured invasively by means of the
SWISS-MODEL Template Library (SMTL) entry for 1rwk.1. Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid
caspase-3 Antibody (E-8) is a mouse monoclonal IgG2a that detects human caspase-3 and full length procaspase-3 by WB and Staining. 488 citations
Kitagawa K, Niikura Y (Apr 2008). "Caspase-independent mitotic death (CIMD)". Cell Cycle. 7 (8): 1001-5. doi:10.4161/cc.7.8. ... 1786 (1): 4-14. doi:10.1016/j.bbcan.2008.07.007. PMC 2581926. PMID 18703117. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS ... 14 (12): 8282-91. doi:10.1128/mcb.14.12.8282. PMC 359367. PMID 7969164. Bolanos-Garcia VM, Kiyomitsu T, D'Arcy S, Chirgadze DY ... 14 (6): 706-14. doi:10.1016/S0955-0674(02)00382-4. PMID 12473343. Zhang Y, Lees E (Aug 2001). "Identification of an overlapping ...
Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder ... Somatic FAS mutations in DNT compartment.[14] 10% of patients. *ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported ... 351 (14): 1409-18. doi:10.1056/NEJMoa040036. PMID 15459302.. [unreliable medical source?] ...
Ng, Tessie M.; Monack, Denise M. (2013). "Revisiting Caspase-11 Function in Host Defense". Cell Host & Microbe. 14 (1): 9-14. ... Geoffrey Mohan (August 14, 2013). "Typhoid Mary case may be cracked, a century later". Los Angeles Times. Retrieved 2015-03-03 ... N. infected more than 200 people over 14 years from 1901 to 1915. At the request of health officials, Mr. N. gave up working in ... 14 (2): 171-182. doi:10.1016/j.chom.2013.07.010. PMC 3785333. PMID 23954156. ...
Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences. 23 (1): 20-26. doi:10.1016/ ... Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, ... 14 (1): 23-31. doi:10.1007/s12192-008-0057-x. PMC 2673901. PMID 18595008. Stirling PC, Cuéllar J, Alfaro GA, El Khadali F, Beh ... 582 (14): 2041-2050. doi:10.1016/j.febslet.2008.04.032. PMID 18442483. S2CID 23147656. Sjölinder M, Björk P, Söderberg E, Sabri ...
Cytoplasmic gelsolin Actin Vitamin D-binding protein Shi, Yigong (2004-08-01). "Caspase activation, inhibition, and ... 259 (14): 8794-8800. ISSN 0021-9258. PMID 6746624. Janmey, Paul A.; Stossel, Thomas P. (1986-10-01). "Kinetics of actin monomer ... 23 (14): 2713-2722. doi:10.1038/sj.emboj.7600280. ISSN 0261-4189. PMC 514944. PMID 15215896. Bohgaki, Miyuki; Matsumoto, Masaki ... 24 (14): 3714-3723. doi:10.1021/bi00335a046. ISSN 0006-2960. PMID 2994715. Doi, Y.; Frieden, C. (1984-10-10). "Actin ...
p53 binds to the third intron of the caspase 6 gene, and promotes the activation of the gene. Caspase 6 in turn activates HIPK2 ... The activity of HIPK2 is increased through the action of caspase 6. Caspase 6 cleaves HIPK2 at residue D916 and D977. As a ... MacLachlan TK, El-Deiry WS (July 2002). "Apoptotic threshold is lowered by p53 transactivation of caspase-6". Proceedings of ... CREB binding protein p53 p300 SKI protein TP53INP1 ATM kinase PIN1 HMGA1 SIAH1 WSB1 caspase 6 Tachykinin receptor 3 Mdm2 CtBP ...
... coli Effector Protein NleF Is a Caspase Inhibitor". PLoS ONE. 8 (3). doi:10.1371/journal.pone.0058937. PMC 3597564. PMID ... For instance, the plant pathogen Pseudomonas syringae has 14 effectors in one strain, but more than 150 have been found in ... Van Engelenburg, Schuyler B; Palmer, Amy E (14 March 2010). "Imaging type-III secretion reveals dynamics and spatial ...
Sbodio JI, Hicks SW, Simon D, Machamer CE (2006). "GCP60 preferentially interacts with a caspase-generated golgin-160 fragment ...
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- ... This protein is involved in caspase-dependent apoptosis and in Parkinson's disease. The gene HTRA2 encodes a serine protease. ... Suzuki Y, Takahashi-Niki K, Akagi T, Hashikawa T, Takahashi R (Feb 2004). "Mitochondrial protease Omi/HtrA2 enhances caspase ...
Wu YH, Shih SF, Lin JY (2004). "Ricin triggers apoptotic morphological changes through caspase-3 cleavage of BAT3". J. Biol. ... 14 (10B): 2121-7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. Stelzl U, Worm U, Lalowski M, et al. (2005). "A human ... 14 (7): 1315-23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747. Colland F, Jacq X, Trouplin V, et al. (2004). "Functional ... 14 (7): 1324-32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). " ...
Plant cells do not have caspases. Plant disease resistance Phytopathogen Plant hormones Systemic acquired resistance ... the pore-forming activity arises from gasdermin B which is cleaved by caspases as a result of the oligomerisation of the NLRs. ... 14 (2): 177-93. doi:10.1016/S0958-1669(03)00035-1. PMID 12732319. Balint-Kurti P (August 2019). "The plant hypersensitive ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... 14 (4): 432-6. doi:10.1016/s0952-7915(02)00354-0. PMID 12088676. Akira S, Uematsu S, Takeuchi O (February 2006). "Pathogen ...
... antagonizes both the precursor and mature forms of Smac and caspase-9". J. Biol. Chem. 280 (1): 174-82. doi:10.1074/jbc. ... "Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function". Nat. Cell Biol. 6 (9): 849-60. doi: ... 14 (6): 801-11. doi:10.1016/j.molcel.2004.05.018. PMID 15200957. Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, ...
2001). A conserved XIAP-interaction motif in caspase-9 and Smac/Diablo regulates caspase activity and apoptosis. Nature. 410: ... "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature. 410 (6824): ... 2001). Isolation and Assay of Caspases. Ch. 1. Methods in Cell Biol. 66:1-27. Profile page at IISER Thiruvananthapuram Faculty ... Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade. Cell, 91(4), 479 ...
... the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, the apoptotic effector caspase, caspase-3, cleaves ICAD and ... Caspase-activated DNase DNA laddering Sakahira, H; Enari, M; Nagata, S (January 1998). "Cleavage of CAD inhibitor in CAD ... When cells are induced to undergo apoptosis, caspase 3 cleaves ICAD to dissociate the CAD:ICAD complex, allowing CAD to cleave ... Cells that lack ICAD or that express caspase-resistant mutant ICAD thus do not show DNA fragmentation during apoptosis, ...
Wu, Y. J. (2004-11-04). "The Chemoprotective Agent N-Acetylcysteine Blocks Cisplatin-Induced Apoptosis through Caspase ...
Codogno P (June 2006). "Autophagy and caspase-independent cell death: p19ARF enters the game". Dev. Cell. 10 (6): 688-9. doi: ... May 2006). "A short mitochondrial form of p19ARF induces autophagy and caspase-independent cell death". Mol. Cell. 22 (4): 463- ... 55 (14): 2988-94. PMID 7606716. Mao L, Merlo A, Bedi G, et al. (July 1995). "A novel p16INK4A transcript". Cancer Res. 55 (14 ... 14 (18): 2358-65. doi:10.1101/gad.827300. PMC 316930. PMID 10995391. Reef S, Zalckvar E, Shifman O, et al. ( ...
Caspase 8 initiates apoptosis by activating "executioner" caspases, numbered 3, 6, and 7. By inhibiting caspase 8, crmA ... The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase-7, thereby inhibiting their activation and ... Inhibition of caspase 8 also prevents cell death signals by ligation of a TNF super family member known as death receptors, ... By inhibiting caspase 1, also known as interleukin 1β converting enzyme (ICE), crmA prevents cytokines interleukin 1β from ...
Betin VM, Lane JD (July 2009). "Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting ... "A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress". ... 122 (Pt 14): 2554-66. doi:10.1242/jcs.046250. PMC 2704886. PMID 19549685. Mariño G, Uría JA, Puente XS, Quesada V, Bordallo J, ...
Betin VM, Lane JD (2009). "Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and ... 122 (Pt 14): 2554-66. doi:10.1242/jcs.046250. PMC 2704886. PMID 19549685. Berthier A, Seguin S, Sasco AJ, Bobin JY, De Laroche ...
"The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ... Note that 14-3-3 binding of Raf enzymes is not necessarily inhibitory: once Raf is open and dimerizes, 14-3-3s can also bind in ... As 14-3-3 proteins are all known to form constitutive dimers, their assemblies have two binding sites. Thus the dimer acts as a ... 57 (14): 2974-8. PMID 9230211. Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, Burns K, Hahne M, Kennedy N, ...
Nakagawa, Akihisa; Sullivan, Kelly D.; Xue, Ding (NaN). "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis ... Lin, K.; Dorman, J. B.; Rodan, A.; Kenyon, C. (14 November 1997). "daf-16: An HNF-3/forkhead family member that can function to ... Check date values in: ,date= (help) Lin, K.; Dorman, J. B.; Rodan, A.; Kenyon, C. (14 November 1997). "daf-16: An HNF-3/ ... Libina, Nataliya (2003-11-14). "Tissue-Specific Activities of C. elegans DAF-16 in the Regulation of Lifespan". Cell. 115 (4): ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn cleaves and activates pro-caspase into ... caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. Accessed 25 March 2007. ...
In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also ... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... "Mitochondrial release of caspase-2 and -9 during the apoptotic process". The Journal of Experimental Medicine. 189 (2): 381-94 ... "The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway". Cell Death and ...
Recently, oocytes were used recently to study the biochemical mechanisms of caspase-2 activation; importantly, this mechanism ... Wang, Fengqin; Shi, Zhaoying; Cui, Yan; Guo, Xiaogang; Shi, Yun-Bo; Chen, Yonglong (2015-04-14). "Targeted gene disruption in ... Dean, S; Marchetti, R; Kirk, K; Matthews, KR (May 14, 2009). "A surface transporter family conveys the trypanosome ... "Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2". Developmental Cell. 16 ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... 2005). "Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2". Structure. 12 (12): 2257-63. doi ... 14 (10B): 2121-7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004 ...
Sinha SK, Chaudhary PM (2004). "Induction of apoptosis by X-linked ectodermal dysplasia receptor via a caspase 8-dependent ...
... induces apoptosis in vitro in human hepatocellular carcinoma Hep 3B cells and might involve caspases and apoptosis ... "Involvement of Caspases and Apoptosis-Inducing Factor in Bufotalin-Induced Apoptosis of Hep 3B Cells". Journal of Agricultural ... 72 (14-15): 1779-85. doi:10.1016/j.phytochem.2011.05.004. PMID 21636103. Müller-Schwarze, D (2006). Chemical ecology of ... Su, CL; Lin, TY; Lin, CN; Won, SJ (14 January 2009). " ...
"Effects of galactomyces ferment filtrate on epidermal barrier marker caspase-14 in human skin cells". Journal of the American ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 274 (14): 9141-8. doi:10.1074/jbc.274.14.9141. PMID 10092585.. *^ Mah AL, Perry G, Smith MA, Monteiro MJ (November 2000). " ... 273 (51): 33909-14. doi:10.1074/jbc.273.51.33909. PMID 9852041.. *^ Kang DE, Soriano S, Frosch MP, Collins T, Naruse S, Sisodia ... 95 (14): 8108-12. Bibcode:1998PNAS...95.8108L. doi:10.1073/pnas.95.14.8108. PMC 20937. PMID 9653148.. ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... G-banding patterns of human chromosome 16 in three different resolutions (400,[14] 550[15] and 850[4]). Band length in this ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... 14 (6): 401-16. doi:10.1038/nrn3505. PMID 23674053. S2CID 2065483.. *^ Terracciano A, Piras MG, Lobina M, Mulas A, Meirelles O ... 96 (14): 7693-96. Bibcode:1999PNAS...96.7693S. doi:10.1073/pnas.96.14.7693. PMC 33603. PMID 10393882.. ... Patten-Hitt E (14 June 2001). "Brain-Derived Neurotrophic Factor (BDNF)". Sciencexpress. The HDLighthouse, Huntington's Disease ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... 14 (2): 115-22. doi:10.1016/j.semcancer.2003.09.016. PMID 15018895. Jechlinger, M.; Sommer, A; Moriggl, R; Seither, P; Kraut, N ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 274 (37): 26008-14. doi:10.1074/jbc.274.37.26008. PMID 10473546.. *^ a b c d Smith DM, Kafri G, Cheng Y, Ng D, Walz T, Goldberg ... 14 (12): 2962-74. doi:10.1016/j.celrep.2016.02.068. PMC 4828729. PMID 26997268.. ...
Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... 60 (14): 756-8. doi:10.1007/BF01716573. PMID 6181289.. *^ Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino ... its autoproteolytic activation and subsequent cleaving of effector caspases, leading to cell apoptosis. ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 14 (7): 723-30. doi:10.1038/nm1784. PMC 2826895. PMID 18587408.. *^ a b Urdinguio RG, Sanchez-Mut JV, Esteller M (November 2009 ... 14 (9): 1171-82. doi:10.1093/hmg/ddi130. PMID 15772088.. *^ a b Riessland M, Ackermann B, Förster A, Jakubik M, Hauke J, Garbes ... 14 (6): 488-92. Bibcode:1996CBio....6.1213A. doi:10.1016/j.cub.2004.03.003. PMID 15043813.. ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... 14 (20): 6874-6885. doi:10.1016/j.bmc.2006.06.042. PMID 16843662. Lepper, Erin R.; Ng, Sylvia S. W.; Gütschow, Michael; Weiss, ... leading to indirect upregulation of caspase-9 activity. Further anti-tumor activity is mediated through the inhibition of ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[27 ... 14 (6): 401-16. doi:10.1038/nrn3505. PMID 23674053.. *^ Terracciano A, Piras MG, Lobina M, Mulas A, Meirelles O, Sutin AR, Chan ... 96 (14): 7693-96. Bibcode:1999PNAS...96.7693S. doi:10.1073/pnas.96.14.7693. PMC 33603. PMID 10393882.. ... Neurotrophins are proteins that help to stimulate and control neurogenesis, BDNF being one of the most active.[13][14][15] Mice ...
Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. ... Caspase 3. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl- ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ... 3 HSD · .4 · .5 · .6 · .7 · .8 · .9 · .10 · .11 · .12 · .13 · .14 · .15 · .16 · .17 · .18 · .19 · .20 · .21 · .22 · .23 · .24 · ... 1 PA · .2 · .3 · .4 · .5 · .6 · .7 · .8 · .9 · .10 · .11 · .12 · .13 · .14 · .15 · .16 · .17 · .18 · .19 · .20 · .21 · .22 α- ... 1 Rsk · .2 PDK · .3 · .4 · .5 · .6 · .7 · .8 · .9 · .10 · .11 · .12 · .13 · .14 · .15 · .16 · DAPK · .18 · .19 · .20 · .21 · . ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ... 14 (19): 2313-2321. doi:10.1038/sj.onc.1201072. PMID 9178907.. *^ Gulbis, Jacqueline M; Kelman, Zvi; Hurwitz, Jerard; O'Donnell ... 1058: 205-14. doi:10.1196/annals.1359.030. PMID 16394138.. *. P. Sankaranarayanan; T. E. Schomay; K. A. Aiello; O. Alter (April ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... 2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-Tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioic acid[2] ... InChI=1S/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+, ... InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12 ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ...
Non obstante, a TRADD únese a FADD, o cal despois recruta a cisteína protease caspase-8. Unha alta concentración de caspase-8 ... Por outra parte, as caspases activadas clivan varios compoñentes da vía NF-κB, incluíndo a RIP, IKK, e as propias subunidades ... Wochenschr. 60 (14): 756-8. PMID 6181289. doi:10.1007/BF01716573.. *↑ Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R ... induce a súa activación autoproteolítica e a subseguinte clivaxe de caspases efectoras, que levan a célula á apoptose. ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ...
Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ... first 14=. (도움말); 지원되지 않는 변수 무시됨: ,last 12=. (도움말); 지원되지 않는 변수 무시됨: ,last 11=. (도움말); 지원되지 않는 변수 무시됨: ,last 14=. (도움말); 지원되지 않는 ... "DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration". 》PNAS》 111 (45): 16082 ... 때문에, 망막색소상피세포는 광변환 후에 변화한 all-트랜스 레테닌을 LRAT[14], RPE65 [15] 등의 효소를 통하여 11-시스 레티닌으로 변환되어, 다시금 광변환 과정을 가능하도록 한다. ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... As noted by Haynes,[14] the subunits of DNA are not endowed with any peculiar kind of quantum mechanical stability, and thus ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... 14] Estes siRNA "secundarios" son estruturalmente distintos dos producidos polo Dicer e parece que son producidos por unha ARN ... elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell 75 (5): 843-54. PMID ... "Genes Dev 18 (14): 1655-66. PMC 478188. PMID 15231716. doi:10.1101/gad.1210204.. ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... Hsp70-14 ? Hsp110[edit]. The Hsp70 superfamily also includes a family of Hsp110/Grp170 (Sse) proteins, which are larger ... 1113 (1): 1-14. Bibcode:2007NYASA1113....1M. doi:10.1196/annals.1391.018. PMID 17513460.. ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... 14. september 1984. Hentet 2. august 2014.. *^ "Nobel Winner Kao Coping with Fame and Alzheimer's". China Daily. 9. oktober ... 1999;14(8):651-661. doi:10.1002/(SICI)1099-1166(199908)14:8,651::AID-GPS992,3.0.CO;2-B. PMID 10489656. ... 1999;14(8):662-7. doi:10.1002/(SICI)1099-1166(199908)14:8,662::AID-GPS993,3.0.CO;2-4. PMID 10489657. ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ...
Caspase. *Caspase 1. *Caspase 2. *Caspase 3. *Caspase 4. *Caspase 5. *Caspase 6 ...
Also, it is extensively used in research for the detection of DNA damage,[34][35] caspase cleavage and apoptosis.[36] In ... Apoptosis (quantification, measurement of DNA degradation, mitochondrial membrane potential, permeability changes, caspase ... Lo, Kenneth; Hahne, Florian; Brinkman, Ryan R.; Gottardo, Raphael (14 May 2009). "flowClust: a Bioconductor package for ... 14] (all freeware), Cellcion, FCS Express, FlowJo, FACSDiva, CytoPaint (aka Paint-A-Gate),[15] VenturiOne, CellQuest Pro, ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor (2015-07-14). "Discrete ... 14][22] These FGF and Shh factors regulate cortical stem cell proliferation and neurogenesis dynamics. Roles for beta-catenin ( ...
"N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases". Nature 457 (7232): 981-989. doi:10.1038/ ... Medpage Today (2008-04-18). Iliwekwa mnamo 2008-06-14. *↑ Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease/ ... doi:10.1002/(SICI)1099-1166(199908)14:8,651::AID-GPS992,3.0.CO;2-B . PMID 10489656 . ... doi:10.1002/(SICI)1099-1166(199908)14:8,662::AID-GPS993,3.0.CO;2-4 . PMID 10489657 . ...
Homo sapiens caspase recruitment domain family member 14 (CARD14), transcript variant 1, mRNA. NCBI Reference Sequence: NM_ ... Homo sapiens caspase recruitment domain family member 14 (CARD14), transcript va... Homo sapiens caspase recruitment domain ... This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase ... See the reference protein sequence for caspase recruitment domain-containing protein 14 isoform 1 (NP_077015.2). ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 2001). "Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 ... "Identification of a new caspase homologue: caspase-14". Cell Death Differ. 5 (10): 838-46. doi:10.1038/sj.cdd.4400444. PMID ...
Rabbit polyclonal Caspase-14 antibody. Validated in WB and tested in Human. Cited in 1 publication(s). Immunogen corresponding ... Believed to be a non-apoptotic caspase which is involved in epidermal differentiation. Seems to play a role in keratinocyte ... Synthetic peptide corresponding to Human Caspase-14 (N terminal).. Database link: P31944 ...
Caspase-14 reveals its secrets. Geertrui Denecker, Petra Ovaere, Peter Vandenabeele, Wim Declercq ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... anti-Caspase Recruitment Domain Family, Member 9 Antikörper * anti-Caspase Recruitment Domain-Containing Protein 18 (ICEBERG) ... anti-Caspase 2, Apoptosis-Related Cysteine Peptidase Antikörper * anti-Caspase 3, Apoptosis-Related Cysteine Peptidase ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... CASP14 encodes a member of the cysteine-aspartic acid protease (caspase) family. Zusätzlich bieten wir Ihnen Caspase 14, ... Show all Caspase 14, Apoptosis-Related Cysteine Peptidase (CASP14) ELISA Kits with Pubmed References. * Human CASP14 ELISA Kit ...
... anti Caspase 14 Antibody is available 2 times from supplier Biovision at Gentaur.com shop ... anti Caspase 9 Antibody 0.2 ml Suppplier: acr. Price: 833.92 USD anti Caspase 1 Antibody 0.2 ml Suppplier: acr. Price: 833.92 ... anti-Caspase 10 Antibody Suppplier: Bluegen antibodies. Price: 563.63 USD anti Caspase 9 Antibody 0.1 Suppplier: acr. Price: ... Anti-Caspase 5 Antibody Suppplier: aviva. Price: 513.93 USD Anti-Caspase 12 antibody Suppplier: Lifescience Market. Price: ...
"Caspase 14" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of ... This graph shows the total number of publications written about "Caspase 14" by people in this website by year, and whether " ... Below are the most recent publications written about "Caspase 14" by people in Profiles. ...
Isolated caspase-14 polypeptides or functional fragments thereof are also provided, as are antibodies that specifically bind ... The invention also relates to an isolated gene encoding caspase-14, as well as functional fragments thereof. The gene or ... In addition, the invention relates to methods of identifying compounds that modulate caspase-14 activity. ... caspase-14 polypeptide or functional fragment thereof, a vector that contains the nucleic acid molecule and a host cell that ...
... a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitmen … ... Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14 ... a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to ... 14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the ...
Caspases are cysteine proteases that play a central role in apoptosis. Therefore they may also be involved in the terminal ... To identify the caspases expressed in normal human epidermis and to define their pattern of expression and activation. ... The mRNAs encoding caspase-1, -2, -3, -4, -6, -7, -8, -9, -10 and -14 were detected by RT-PCR. Accordingly, the ... However, only procaspase-1 and the processed caspase-14 were detected in extracts of superficial SC. In addition to these two ...
... cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all ... Meanwhile, the efficacy of DAP in reducing the apoptotic cells was lost after using the inhibitor of caspase-3 or caspase-9 but ... However, DAP had no inhibitory effect on caspase-8 activity and cleaved caspase-8 production. ... Furthermore, the silencing of caspase-9 reduced the yield of nucleoprotein (NP) and disabled the inhibitory ability of DAP in ...
A Correction to the Perspective Titled Caspase-8 for Outer Harmony by G. Sollberger and H.-D. Beer ... A Correction to the Perspective Titled "Caspase-8 for Outer Harmony" by G. Sollberger and H.-D. Beer ... A Correction to the Perspective Titled "Caspase-8 for Outer Harmony" by G. Sollberger and H.-D. Beer ... A Correction to the Perspective Titled "Caspase-8 for Outer Harmony" by G. Sollberger and H.-D. Beer ...
Active Motifs Caspase-14 antibody (mAb) (Clone 70A1426) was raised in a Mouse host. It has been validated for use in Western ... Active Motifs Caspase-14 antibody (mAb) (Clone 70A1426) was raised in a Mouse host. It has been validated for use in Western ...
Bertin J et al. (2001) CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase ( ... Caspase-recruitment-Domain-enthaltendes Protein 14. Das CARD14-Gen kodiert ein Protein das mit verschiedenen Proteinen bei der ...
This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase ...
Should the Rat Caspase 14 (CASP14) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. ... Should the Rat Caspase 14 (CASP14) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. ... Should the Human Caspase 14 (CASP14) ELISA Kit is proven to show malperformance, you will receive a refund or a free ... Should the Human Caspase 14 (CASP14) ELISA Kit is proven to show malperformance, you will receive a refund or a free ...
Pharmacological Actions : Apoptotic, Bcl-2 protein down-regulation, Caspase-3 Activation, Caspase-8 activation, Caspase-9 ... Pharmacological Actions : Apoptotic, Caspase-3 Activation, Caspase-8 activation, Caspase-9 Activation, Cell cycle arrest ... Pharmacological Actions : Apoptotic, Caspase-3 Activation, Caspase-8 activation, Caspase-9 Activation, NADPH Oxidase Inhibitors ... Pharmacological Actions : Antiproliferative , Apoptotic, Caspase-3 Activation, Caspase-8 activation, Caspase-9 Activation, Cell ...
High specificity and sensitivity Rat Caspase-14 qPCR primer pair is designed by proprietary primer design algorithm and ... Unlike the other short prodomain caspases(caspase-3, caspase-6, and caspase-7), Caspase 14 was not processed by multiple death ... Marc Van De Craen, et al. (1998) Identification of a new caspase homologue: caspase-14. Cell death differ. 5(10): 838-46. ... Caspase 14 is a member of the caspase family. Caspases are a kind of cysteine proteinase consisting of a prodomain plus large ...
Phage display reveals peptides that bind to the caspase-6 zymogen, inducing its tetramerization and specifically inhibiting its ... Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity *Agne ... Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization. *Karen Stanger1. *, Micah Steffek2. n5*, Lijuan ... Self-activation of caspase-6 in vitro and in vivo: caspase-6 activation does not induce cell death in HEK293T cells. . Biochim ...
Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether ... Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies. Tait and ... MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing ... colleagues show that caspase-independent cell death induced by mitochondrial permeabilization stimulates NF-κB activity through ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered Inflammatory Caspases.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...
X. Zhao et al., Caspase-2 cleavage of tau reversibly impairs memory. Nat. Med. 10.1038/nm.4199 (2016). [Abstract] ... Preventing caspase-2 cleavage of tau blocks memory impairment in an animal model of Alzheimers disease. ... Preventing caspase-2 cleavage of tau blocks memory impairment in an animal model of Alzheimers disease. ... Importantly, decreasing caspase-2 beneficially impacted long-term memory in a mouse model of AD. ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum (PubMed: ... caspase 14. Enable Javascript to view the expand/collapse boxes.. Open All Close All ...
TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and ... Caspase-independent cell death. Nat Med. 2005;11:725-30.CrossRefPubMedGoogle Scholar ... Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells ... Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid ...
CAPE also induced active caspase-3 expression in CD4+ T cells; CCR4+CD4+ T cells were more sensitive to CAPE induction than ... S5. Caffeic acid phenethyl ester (CAPE) induces active caspase-3 expression in polarized T helper type 1 (Th1) and Th2 cells. ... Caffeic acid phenethyl ester inhibits nuclear factor-κB and protein kinase B signalling pathways and induces caspase-3 ... Cells were stained with monoclonal antibodies for CD4 and active caspase-3 and then analysed by flow cytometry. Results are ...
Objective We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the ... Targeting caspase-1 by inhalation-therapy: effects of Ac-YVAD-CHO on IL-1β, IL-18 and downstream proinflammatory parameters as ... Mathiak G, Grass G, Herzmann T, Luebke T, Zetina CC, Boehm SA, Bohlen H, Neville LF, Hoelscher AH (2000) Caspase-1-inhibitor ac ... We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the potential to ...
Molecular Docking Analysis of Caspase-3 Activators as Potential Anticancer Agents.. Kashaw SK, Agarwal S, Mishra M, Sau S, Iyer ... Pharmacophore Modeling, Docking and Molecular Dynamics Studies on Caspase-3 Activators Binding at β-Tubulin Site. Bhunia SS et ... Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinsons Disease. Yuan J et al. PLoS ... Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. Sharma S et al. Biomed Res Int. (2013 ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ...
The function of caspase 4 is not fully known, but it is believed to be an inflammatory caspase, along with caspase 1, caspase 5 ... The Proteolysis Map Caspase Martinon F, Tschopp J (2007). "Inflammatory caspases and inflammasomes: master switches of ... Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family ... Smith C, Soti S, Jones Torey A, Nakagawa A, Xue D, and Yin H (2017). "NSAIDs are Caspase Inhibitors". Cell Chem Biol. 24 (3): ...
  • Caspases are a family of cysteine proteases that play an essential role in carrying out apoptosis. (gentaur.com)
  • Caspases are cysteine proteases that play a central role in apoptosis. (ovid.com)
  • The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. (nature.com)
  • Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family of cysteine proteases called caspases. (wikipedia.org)
  • We examined the temporal profile of apoptosis after fluid percussion-induced traumatic brain injury (TBI) in rats and investigated the potential pathophysiological role of caspase-3-like proteases in this process. (jneurosci.org)
  • Together, these results implicate caspase-3-like proteases in neuronal apoptosis induced by TBI and suggest that the blockade of such caspases can reduce post-traumatic apoptosis and associated neurological dysfunction. (jneurosci.org)
  • Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. (rcsb.org)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • Caspases are a family of cysteine proteases which are the major executors of apoptosis and inflammation. (iucr.org)
  • CASP14 caspase 14, apoptosis-related cysteine peptidase BackgroundCaspases are a family of cysteine proteases that are key mediators of programmed cell death or apoptosis.1 The precursor form of all. (craftstylish.com)
  • Apoptosis requires the action of various classes of proteases, including a family of cysteine proteases known collectively as the caspases. (ahajournals.org)
  • Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). (sciencemag.org)
  • A number of substrates for the caspase proteases have now been identified, including protein kinases ( 3 ), the retinoblastoma protein ( 4 ), cytoskeletal proteins ( 5 ), and several autoantigens ( 6 ). (sciencemag.org)
  • Caspase is a family of cysteine proteases, with specific cysteine residue that cleaves proteins after the aspartic acid residue, a specificity which is not normal among proteases to produce the active mature caspases [5]. (thefreelibrary.com)
  • 3) zinc deficiency activation of calpain and caspase proteases, leading to cell death. (arvojournals.org)
  • Calpain inhibitor, SNJ-1945, and pan-caspase inhibitor, z-VAD-fmk, were used to confirm activation of the proteases. (arvojournals.org)
  • The proteins that execute the apoptotic programme are a group of proteases termed caspases (cysteine‐dependent aspartate‐specific protease). (els.net)
  • Apoptotic caspases are cysteine proteases that become activated in response to diverse extracellular and intracellular stimuli and subsequently carry out the cell death programme by systematically cleaving intracellular proteins. (els.net)
  • Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of normal embryonic and fetal development. (biologists.org)
  • Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. (nature.com)
  • This has spurred substantial efforts to develop caspase inhibitors for clinical use, yet safety issues such as tumor growth during or after treatment are a concern, and none have currently been approved. (sciencemag.org)
  • lends additional weight to the prospect of specifically targeting the activity of caspase-2 in AD, although the development of safe and effective caspase inhibitors that show promise in animal models remains a significant challenge. (sciencemag.org)
  • Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. (springer.com)
  • Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. (nih.gov)
  • We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. (rcsb.org)
  • However, it was practically difficult to do so mainly because caspase inhibitors are not specific for each substrate. (nii.ac.jp)
  • We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. (jimmunol.org)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • Pretreatment of ovarian cancer cells and their whole cell lysate with tetrapeptide inhibitors of caspases in vitro significantly decreased Akt cleavage induced by cisplatin and exogenous active caspase-3. (aacrjournals.org)
  • Consistent with this finding, caspase-2 exists as a (p19/p12)2 dimer in solution, even in the absence of substrates or inhibitors. (nih.gov)
  • This study was undertaken to investigate the effect of 2 caspase inhibitors, Z-VDVAD-FMK and Z-DEVD-FMK, in the protection of endothelial cells from OxyHb-induced apoptosis. (ahajournals.org)
  • Methods -Cultured bovine brain microvascular endothelial cells (passages 5 to 9) were exposed to OxyHb (10 μmol/L) for 24 to 72 hours with and without caspase inhibitors. (ahajournals.org)
  • Cell attachment, DNA ladder, Western blotting of poly(ADP-ribose) polymerase (PARP), and caspase activities were measured to confirm the cytotoxic effect of OxyHb and the protective effect of the caspase inhibitors. (ahajournals.org)
  • Caspase inhibitors attenuated the cytotoxic effect of OxyHb. (ahajournals.org)
  • In this study we investigated the effect of OxyHb on the activities of caspase-2 and -3 and the prophylaxis effect of caspase inhibitors on OxyHb-induced apoptosis in bovine brain microvessel endothelial cells. (ahajournals.org)
  • During treatments with caspase inhibitors and OxyHb, the cells were incubated in CS-C Medium (Cell Systems Corporation) without growth factor and with 1% (vol/vol) fetal bovine serum. (ahajournals.org)
  • After human CNE2 cells were treated with 100 μM DATS and inhibitors (10 μM SB203580 and Z-LETD-FMK for p38MAPK and caspase-8, respectively), changes in cell viability and apoptosis and in p38MAPK and caspase-8 activity were detected. (scielo.br)
  • The results indicated that DATS activates p38MAPK and caspase-8, but both inhibitors have an effect on P38MAPK and caspase-8 activity. (scielo.br)
  • Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. (biologists.org)
  • However, inhibitors of these caspases could not protect the cells completely from ALSL-induced apoptosis. (springer.com)
  • To determine whether neuronal death is necessary for the recruitment of new neurons, we infused caspase inhibitors into HVC in vivo and suppressed neurodegeneration for at least 20 d after the transition to nonbreeding conditions. (washington.edu)
  • Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. (jneurosci.org)
  • At first, we postulated to suppress neuronal death by inhibition of caspases. (nii.ac.jp)
  • We and other investigators showed that the immunosuppressive effects of the Western antirheumatic drug (ARD), HCQ, and of Chinese ARDs, tetrandrine (Tet) and Tripterygium wilfordii hook F (TWHf), were mediated through both the inhibition of T cell activation and the induction of T cell apoptosis ( 12 , 13 , 14 , 15 ). (jimmunol.org)
  • The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP), spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. (frontiersin.org)
  • To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1 G93A ). (sciencemag.org)
  • Caspases play an instrumental role in neurodegeneration in transgenic mSOD1 G93A mice, which suggests that caspase inhibition may have a protective role in ALS. (sciencemag.org)
  • All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. (portlandpress.com)
  • The retention of Spi-2 proteins' caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread. (portlandpress.com)
  • Taken together, the results indicate that XIAP prevents apoptosis through a PI 3-K-dependent inhibition of the caspase cascade. (aacrjournals.org)
  • In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. (rupress.org)
  • We show here that inhibition of proteasomal degradation results in an increased oligomerization and activation of caspase-8 on the cytosolic side of intracellular membranes. (asm.org)
  • We went on to study the molecular mechanism and significance of caspase-8 activation in response to proteasome inhibition. (asm.org)
  • The above results indicate that MUC1 gene silencing induces growth inhibition in SMMC‑7721 cells through Bax‑mediated mitochondrial and caspase-8-mediated death receptor apoptotic pathways. (spandidos-publications.com)
  • These effector fragments may become newly active (as in the case of caspase‐mediated cleavage of ROCK1) or may act to inhibit normal protein function (e.g. caspase‐mediated cleavage of IKB renders the protein resistant to proteosomal degradation and thus allows for sustained inhibition of NFκB, see text for details). (els.net)
  • Inhibition of caspase activity in wing discs reduced wing size demonstrating functional significance. (elifesciences.org)
  • Accordingly, the immunohistological analyses showed clear expression in the epidermis of the corresponding proteins except caspase-2 and caspase-8, with only a weak expression of caspase-9. (ovid.com)
  • Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restraints on cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormally growing cells. (wikipedia.org)
  • NLR proteins are essential for activation of caspase-1 by various bacteria, such as Salmonella typhimurium , Staphylococcus aureus , and Listeria monocytogenes and are involved in sensing of bacterial cell wall products ( 8 , 9 ). (pnas.org)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • 0.05-0.001) enhanced apoptosis of DU145 and LNCaP cells with induction of a higher ratio of Bax/Bcl-2 proteins, disruption of mitochondrial membrane potential, and activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. (portlandpress.com)
  • For example, in apoptosis, caspases promote cell death via cleavage of key structural and enzymatic proteins that in some instances is inhibited by phosphorylation near the scissile bond. (mcponline.org)
  • In this study, we systematically investigated how protein phosphorylation affects susceptibility to caspase cleavage using an N-terminomic strategy, namely, a modified terminal amino isotopic labeling of substrates (TAILS) workflow, to identify proteins for which caspase-catalyzed cleavage is modulated by phosphatase treatment. (mcponline.org)
  • To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. (asm.org)
  • Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death. (asm.org)
  • We and others have reported that caspase-3 cleaves Bcl-2 at Asp-34 and Bcl-x L at Asp-61 and Asp-76 to produce N-terminally truncated proteins that have lost their antiapoptotic activities ( 8 , 13 , 20 , 22 , 35 ). (asm.org)
  • In the context of cellular apoptosis, it has been shown previously that caspase-3 activation, a hallmark of mitochondrial dysregulation, promotes hydrolysis of several key cellular proteins. (biomedsearch.com)
  • Cleavage of these proteins by caspases may either activate or inactivate essential functions or produce cleavage products with altered activities. (sciencemag.org)
  • This caspase-8 initiates other downstream proteins including procaspase-3 in two ways: the first is a complex pathway, wherein caspase8 cleaves Bcl-2 interacting protein named Bid and also releases cytochrome-c. (thefreelibrary.com)
  • In the family, Caspase-3 in its inactive zymogens, pro-caspase-3 is a remarkable protein as the enzyme shows a large substrate diversity, as a variety of proteins have been cleaved in cell maintenance. (thefreelibrary.com)
  • Substrates targeted by caspases during the apoptotic programme include proteins involved in maintaining various aspects of cytoskeletal and organelle architecture as well as proteins that function in signalling networks critical for cell function. (els.net)
  • Caspase‐mediated cleavage of target proteins may produce stable functional effector fragments or unstable fragments that are quickly degraded. (els.net)
  • For the initiator caspases, binding to adaptor proteins results in the cleavage of the prodomain and subsequent rearrangement of the large and small subunits to produce a catalytically active heterodimer. (els.net)
  • Once active, caspase 9 functions to proteolytically cleave and activate the effector caspases 3 and 7, which then go on to cleave numerous intracellular proteins to dismantle the cell. (els.net)
  • a) Caspase‐mediated cleavage of intracellular proteins may result in the production of stable, functionally active effector fragments. (els.net)
  • Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene. (wikipedia.org)
  • The CASP14 gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • You need info about Human Caspase-14 (CASP14) ELISA Kit or any other Gentaur produtct? (gentaurshop.com)
  • Should the Human Caspase 14 (CASP14) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. (scalegen.com)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Caspase 14 (CASP14) in samples from tissue homogenates, cell lysates or other biological fluids. (scalegen.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Caspase 14 (CASP14) in tissue homogenates, cell lysates and other biological fluids. (scalegen.com)
  • This assay has high sensitivity and excellent specificity for detection of Caspase 14 (CASP14). (biotecnika.org)
  • No significant cross-reactivity or interference between Caspase 14 (CASP14) and analogues was observed. (biotecnika.org)
  • Intra-assay Precision (Precision within an assay): 3 samples with low, middle and high level Caspase 14 (CASP14) were tested 20 times on one plate, respectively. (biotecnika.org)
  • 14-Deoxy-11,12-didehydroandrographolide inhibits apoptosis in influenza A(H5N1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity. (physiciansweekly.com)
  • Overall results suggest that DAP exerts its antiviral effects by inhibiting H5N1-induced apoptosis on the caspase-9-dependent intrinsic/mitochondrial pathway, which may be one of the anti-H5N1 mechanisms of DAP. (physiciansweekly.com)
  • Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML xenograft tumor growth in vivo. (springer.com)
  • Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
  • We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
  • Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. (jimmunol.org)
  • Caspase-3, caspase-7, and caspase-8 are important caspases in the apoptosis pathway and play an important role in the development and progression of cancer. (aacrjournals.org)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • The results of our study suggested that NE is an important factor in OA, which induces chondrocyte apoptosis and facilitates the occurrence of OA via caspase signaling pathway, and targeting the crucial signal centering around NE may be the potential therapies for OA. (frontiersin.org)
  • Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. (sciencemag.org)
  • Pretreatment with the pan-caspase inhibitor z-VAD-fmk partially, but significantly, blocked the berberine-induced apoptosis, as also confirmed by the comet assay analysis of DNA fragmentation, suggesting that berberine-induced apoptosis of human prostate cancer cells is mediated primarily through the caspase-dependent pathway. (aacrjournals.org)
  • Cytotoxic stress, such as that caused by cancer therapies, leads to activation of caspase-2, which acts as a direct effector of the mitochondrion-dependent apoptotic pathway resulting in programmed cell death. (nih.gov)
  • These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function. (rupress.org)
  • ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. (spandidos-publications.com)
  • Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s). (asm.org)
  • On the other hand, the extrinsic cell death pathway involves the activation of caspase 8 through binding to the adaptor protein Fas-associated protein with death domain (FADD), which in turn activates caspase 3 to facilitate cell death. (asm.org)
  • In conclusion, microwave radiation induced neural cell apoptosis via the classical mitochondria-dependent caspase-3 pathway. (medsci.org)
  • In the second simple pathway, caspase-8 cleaves procaspase-3 directly and activates it. (thefreelibrary.com)
  • Its nature as a cell-free extract system allows substrates to be very simply added by pipette, and their effects on apoptosis and caspase activation and their placement in the apoptotic signaling pathway (e.g., pre- or post-mitochondrial) are subsequently very simply studied using the techniques described in this chapter. (springer.com)
  • Hypoxia activated the calpain pathway, while A2E activated both calpain and caspase pathways in monkey RPE cells. (arvojournals.org)
  • Caspase activation may proceed through either an external (extrinsic) or internal (intrinsic) death pathway, dependent on the stimulus. (els.net)
  • Depending on the structure of the prodomain and their function, caspases are typically divided into 3 major groups (Figure 1 A). The caspases with large prodomains are referred to as inflammatory caspases (group I) and initiator of apoptosis caspases (group II), while caspases with a short prodomain of 20-30 amino acids are named effector caspases (group III). (jci.org)
  • During apoptosis in humans, initiator caspases integrate molecular signals into proteolytic activity ( 11 ) and subsequently activate the downstream effector caspases, thus transmitting and amplifying the apoptotic signal ( 12 ). (aacrjournals.org)
  • Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. (mdpi.com)
  • There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
  • Several initiator caspases are known to be activated upstream of the mitochondrial dysfunction by specific apoptotic stimuli. (rupress.org)
  • The formation of active caspases forms a cascade in which initiator caspases (8, 9) interact with the downstream effector molecules (3, 7) to facilitate their own activation. (thefreelibrary.com)
  • Chen M, Wang J (2002) Initiator caspases in apoptosis signaling pathways. (springer.com)
  • A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases. (els.net)
  • The prodomain of the initiator (also known as apical) caspases (2, 8, 9 and 10) is much longer than that of effector caspases 3, 6 and 7. (els.net)
  • Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the prodomain, large and small subunits. (els.net)
  • Cytoplasmic cytochrome c drives the formation of the apoptosome and activation of initiator caspase 9. (els.net)
  • The binding of extracellular ligands to death receptors triggers the formation of a DISC complex resulting in the activation of initiator caspases 8 and/or 10. (els.net)
  • These studies uncovered a nonapoptotic role for the initiator caspase-9 in primitive blood formation. (biologists.org)
  • These data reveal a novel nonapoptotic function for the initiator caspase-9 and, for the first time, implicate nonapoptotic caspase activity in primitive blood formation. (biologists.org)
  • Caspase-14 Is a Novel Developmentally Regulated Protease," The Journal of Biological Chemistry 273(45): 29648-29653, 1998. (patentgenius.com)
  • Caspases ( c ysteine- asp artic prote ases , c ysteine asp art ases or c ysteine-dependent asp artate-directed prote ases ) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis , pyroptosis and necroptosis ) and inflammation . (wikipedia.org)
  • They are named caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. (wikipedia.org)
  • Secretion of IL-1β, −18, and −33 by activated macrophages depends on the protease caspase-1 that converts their precursors to the mature and biologically active cytokines ( 1 , 2 ). (pnas.org)
  • Caspase-8 is a cysteine protease, which cleaves downstream substrates such as effector caspases, to initiate the apoptotic cascade and transmit apoptotic signals downstream of death receptors ( 16 ). (aacrjournals.org)
  • Caspase 6 (CASP6) is a neuron degeneration-related protease and is widely considered to be a potential drug-design target against neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. (iucr.org)
  • The cell death protease caspase-2 has recently been recognized as the most apical caspase in the apoptotic cascade ignited during cell stress signaling. (nih.gov)
  • CASP3 caspase 3, apoptosis-related cysteine peptidase BackgroundThis gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. (craftstylish.com)
  • A new independent 54 page research with title 'Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) - Pipeline Review, H2 2017'guarantees you will remain better informed than your competition. (medgadget.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) pipeline Target constitutes close to 6 molecules. (medgadget.com)
  • The latest report Caspase 7 - Pipeline Review, H2 2017, outlays comprehensive information on the Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (rupress.org)
  • The protease family of the caspases, the mammalian homologues of the Caenorhabditis elegans death gene, is required for mammalian apoptosis. (ahajournals.org)
  • Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade," Cell , vol. 91, no. 4, pp. 479-489, 1997. (hindawi.com)
  • The P4 position of caspase cleavage sites confers protease specificity ( 10 ). (sciencemag.org)
  • Li P, Nijhawan D, Budihardjo I (1997) Cytochrome c and dATP dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. (springer.com)
  • We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1β processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. (pnas.org)
  • In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. (frontiersin.org)
  • Conclusions -OxyHb activates caspase-2 and -3 in cultured brain microvessel endothelial cells. (ahajournals.org)
  • or calpain activates downstream caspase cascade ( Nakagawa and Yuan, 2000 ). (rupress.org)
  • This, in turn, activates downstream death programs, such as caspase 3 and poly(ADP-ribose) polymerase (PARP). (asm.org)
  • This procaspase-9 comes and activates caspase-9 and simultaneously this activates procaspase-3 and then activates caspase-3. (thefreelibrary.com)
  • The binding of Fas ligand to Fas recruits caspase 8 to Fas via an adaptor, FADD/MORT1, and activates a caspase cascade leading to apoptosis. (pubmedcentralcanada.ca)
  • Pro-caspase 8 is processed at the DISC to the mature active enzyme, and activates other caspases, such as caspase 3, in the downstream of the caspase cascade. (pubmedcentralcanada.ca)
  • Truncated Bid (tBid) then activates Bax/Bak which induce mitochondrial permeabilisation, the release of cytochrome c , formation of the apoptosome and the activation of caspases 9 and 3. (els.net)
  • Figure 2: MOMP induces TNF synthesis under caspase-deficient conditions. (nature.com)
  • MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. (pnas.org)
  • Importantly, Bacillus anthracis infection induces IL-1β secretion in a manner that depended on caspase-1 and NOD2. (pnas.org)
  • Although doxorubicin may initiate apoptotic program by using molecules such as p53, reactive oxygen species, and caspases ( 7 , 8 ), the detailed mechanism by which doxorubicin induces apoptosis has not been fully clarified. (aacrjournals.org)
  • Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. (biomedsearch.com)
  • These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity. (biomedsearch.com)
  • Our results unveiled a previously unknown mechanism through which disruption of protein homeostasis induces caspase-8 oligomerization, activation, and apoptosis. (asm.org)
  • Our results indicate the tetrandrine induces apoptosis and autophagy of SAS human cancer cells via caspase-dependent and LC3-I and LC3-II‑dependent pathways. (spandidos-publications.com)
  • Based on these findings, we conclude that etoposide induces loss in cell viability by inducing mitochondrial dysfunction, caspase-3 activation and degradation of FTase/GGTase α-subunit. (biomedsearch.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Both pathways finally end up in the level of activation of caspases for cell death. (thefreelibrary.com)
  • Taken together, our results indicate that ALSL-induced apoptosis of A375 cells is mediated by both mitochondrial caspase-dependent and -independent pathways and it involves ROS and JNK activation in the mitogen-activated protein kinase cascade. (springer.com)
  • Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. (springer.com)
  • These results suggested that Fas-associated protein with death domain can kill the cells via two pathways, one mediated by caspases and another that does not involve them. (pubmedcentralcanada.ca)
  • Activation of caspases through intrinsic and extrinsic death pathways. (els.net)
  • Caspase-1 cleaves GSDMD, but whether this process contributes to neuroinflammation is unknown. (pnas.org)
  • Out of the complex DFF40 and DFF45 (DNA fragmentation factor 45), the caspase-3 cleaves DFF45 and as a result of that, DFF45 dissociates from DFF40, causing oligomerization of DFF40 which has DNase activity. (thefreelibrary.com)
  • group III: apoptosis effector caspases. (jci.org)
  • The three effector caspases are expressed as dimeric zymogens and each monomer contains a short pro-domain, a large subunit (p20), an intersubunit linker (L) and a small subunit (p10). (iucr.org)
  • However, the pro-domains of effector caspases are considered to have no such function for two reasons. (iucr.org)
  • Following cleavage of a target protein by effector caspases, there are several probable functional consequences. (els.net)
  • Transcript profiling studies identified c aspase (zeige GATA3 ELISA Kits )-14 a s a novel downstream target of Gata-3, in keeping with its roles in different iation (zeige GATA3 ELISA Kits ) and tumorigenesis. (antikoerper-online.de)
  • We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the potential to attenuate the pulmonary and systemic release of the caspase-1-dependent cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) as well as their downstream enzymes iNOS and COX-2 in rat experimental endotoxaemia. (springer.com)
  • Further downstream, caspase-8 triggers the proteolytic activation of other caspases and cleavage of cellular substrates. (rupress.org)
  • Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. (sciencemag.org)
  • The observed casp9 activity in the ventral blood island (VBI) turns out to be independent of the activity of the downstream effectors casp3 and caspase-7 (casp7). (biologists.org)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • This Review gives an overview of caspases and their classification, structure, and substrate specificity. (jci.org)
  • In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF (PubMed:16854378, PubMed:19960512). (nih.gov)
  • The cell death was associated with activation of caspase 3, nuclear translocation of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. (asm.org)
  • Here, we investigated the possibility that Bcl-2 could also serve as a caspase substrate. (sciencemag.org)
  • The EarlyTox ™ Caspase-3/7 NucView ™ 488 Assay Kits enable detection of apoptosis in intact cell populations through use of NucView 488 Caspase-3 substrate. (moleculardevices.com)
  • This substrate consists of a fluorogenic DNA dye coupled to the caspase-3/7 DEVD recognition sequence. (moleculardevices.com)
  • Initially non-fluorescent, it permeates the cell membrane, and if the cell is apoptotic, the substrate is cleaved by caspase-3/7, releasing a dye that enters the nucleus and binds to DNA, resulting in bright green fluorescence. (moleculardevices.com)
  • The two dyes are separated by a cleavable peptide substrate for caspase-3, a diagnostic enzyme that is upregulated in dying cells. (spiedigitallibrary.org)
  • In the native form, LS498 fluorescence is quenched until caspase-3 cleavage of the peptide substrate. (spiedigitallibrary.org)
  • Fluorogenic caspase-3 substrate. (fishersci.com)
  • This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) famil. (nih.gov)
  • Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). (nih.gov)
  • Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
  • Of 35 selected single-nucleotide polymorphisms, four in the caspase-7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk for endometrial cancer. (aacrjournals.org)
  • No association was observed between polymorphisms of the caspase-8 gene and risk for endometrial cancer. (aacrjournals.org)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. (biomedsearch.com)
  • Further investigation using western blotting revealed that cytochrome c was released from the mitochondria into the cytoplasm, and caspase‑8 and caspase‑9 were activated in MUC1 gene‑silenced SMMC‑7721 cells. (spandidos-publications.com)
  • In addition, results from the co‑immunoprecipitation experiments demonstrated that the MUC1 cytoplasmic tail can bind directly to Bax or caspase‑8 and these interactions were reduced upon MUC1 gene silencing in SMMC‑7721 cells. (spandidos-publications.com)
  • We designed a caspase-reporting system based on the transcriptional induction of the eGFP gene. (biologists.org)
  • We compared the caspase specificity of CrmA to three orthologs from orthopoxviruses and four from more distant chordopoxviruses. (portlandpress.com)
  • The structure reveals the hydrophobic properties of the S5 specificity pocket, which is unique to caspase-2, and provides the details of the inhibitor-protein interactions in subsites S1-S4. (nih.gov)
  • These features form the basis of caspase-2 specificity and allow the design of caspase-2-directed ligands for medical and analytical use. (nih.gov)
  • See the reference protein sequence for caspase recruitment domain-containing protein 14 isoform 1 (NP_077015.2). (nih.gov)
  • Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous antiapoptotic protein. (aacrjournals.org)
  • One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. (rupress.org)
  • Binding of these two components presumably leads to a conformational change in Apaf-1 and exposes the so-called caspase recruitment domain (CARD). (rupress.org)
  • Zusätzlich bieten wir Ihnen Caspase 14, Apoptosis-Related Cysteine Peptidase Kits (49) und Caspase 14, Apoptosis-Related Cysteine Peptidase Proteine (17) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • After DAP treatment, the protein expression levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all obviously downregulated. (physiciansweekly.com)
  • Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. (springer.com)
  • 2) OxyHb increased caspase-2 and -3 activities, produced DNA ladders, and cleaved PARP in endothelial cells. (ahajournals.org)
  • 3) Z-VDVAD-FMK and Z-DEVD-FMK (100 μmol/L) attenuated OxyHb-induced cell detachment, reduced caspase-2 and -3 activities, abolished OxyHb-induced DNA ladders, and prevented OxyHb-induced cleavage of PARP. (ahajournals.org)
  • Atg-5, beclin-1 siRNA decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells and protected tetrandrine-treated SAS cells against decrease in cell viability. (spandidos-publications.com)
  • Chloroquine, NAC and bafilomycin A1 also decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells. (spandidos-publications.com)
  • The expressions of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and PARP were examined by immunoblotting or immunocytochemistry. (medsci.org)
  • Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c, cleaved caspase-3 and PARP all increased. (medsci.org)
  • Caspases are activated by various apoptotic stimuli and cleave cellular substrates such as poly(ADP-ribose) polymerase (PARP), 1 lamin, actin, p27, and inhibitor of caspase-activated DNase, which is responsible to cause morphological changes of nuclei, and degradation of chromosomal DNA. (pubmedcentralcanada.ca)
  • Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
  • The large and small subunit associate with each other to form an active heterodimer caspase. (wikipedia.org)
  • Caspases, a family of c ysteinyl a spartate- s pecific p rote ases , are synthesized as zymogens with a prodomain of variable length followed by a large subunit (p20) and a small subunit (p10). (jci.org)
  • We report herein that exposure of insulin-secreting INS 832/13 cells or normal rat islets to etoposide leads to significant activation of caspase-3 and subsequent degradation of the common α-subunit of farnesyl/geranylgeranyl transferases (FTase/GGTase). (biomedsearch.com)
  • In addition, treatment of cell lysates with recombinant caspase-3 also caused FTase/GGTase α-subunit degradation. (biomedsearch.com)
  • Moreover, nifedipine, a calcium channel blocker, markedly attenuated etoposide-induced caspase-3 activation, FTase/GGTase α-subunit degradation in INS 832/13 cells and normal rat islets. (biomedsearch.com)
  • All caspases are produced as catalytically inactive zymogens or proenzymes containing a prodomain, a large (p20) and a small subunit (p10). (els.net)
  • Subsequently, active caspases specifically process various substrates that are implicated in apoptosis and inflammation. (jci.org)
  • Caspases lead to the proteolysis of a number of cellular substrates, a process which finally results in the apoptotic collapse of the cell. (rupress.org)
  • Caspases proteolytically cleave a host of cellular substrates at aspartate residues, which may render them either functionally inactive or confer novel activities that help to promote cellular demise. (els.net)
  • Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. (rupress.org)
  • z-VAD-fmk inhibited caspase activation, suggesting no interaction between calpain and caspases. (arvojournals.org)
  • DN caspase-9 (provided courtesy of Emad S. Alnmeri, Thomas Jefferson University, Philadelphia, PA) has been reported to inhibit the caspase cascade ( 5 ). (cdc.gov)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (uniprot.org)
  • Caspase is an inactive enzyme zymogen under normal circumstances, but once activated it will trigger the caspase cascade, eventually leading to apoptosis. (scielo.br)
  • The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier. (wikipedia.org)
  • Believed to be a non-apoptotic caspase which is involved in epidermal differentiation. (abcam.com)
  • Caspase-14 may not play a role in apoptosis, but instead may regulate keratinocyte differentiation. (gentaur.com)
  • Caspase-14 may also be responsible for proteolytic processing of filaggrin during terminal differentiation of keratinocytes. (gentaur.com)
  • A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES. (umassmed.edu)
  • Identification of a New Caspase Homologue: Caspase-14," Cell Death and Differentiation 5: 838-846, 1998. (patentgenius.com)
  • This confirms that only caspase-14 is involved in keratinocyte differentiation, and suggests that keratinocytes are ready to induce apoptosis in response to cutaneous damage. (ovid.com)
  • There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing. (wikipedia.org)
  • Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation. (wikipedia.org)
  • Caspase-3 activation is a cell requirement during early stages of the skeletal myoblast differentiation. (wikipedia.org)
  • Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
  • Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
  • The expression and processing of this caspase may take part in keratinocyte terminal differentiation, which is essential for the skin barrier. (sinobiological.com)
  • Non-apoptotic caspase involved in epidermal differentiation. (nih.gov)
  • Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is also required for developmental processes such as lymphoid proliferation and erythroid differentiation. (rcsb.org)
  • Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (wikipedia.org)
  • Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
  • The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer. (wikipedia.org)
  • The anti-inflammatory drug indoprofen is an inhibitor of the activity of the caspase-4 enzyme. (wikipedia.org)
  • The presence of Thr 152 in the conserved loop introduces a "kill switch" in mammalian caspase-3, whereas the more ancient Ser 150 reduces without abolishing enzyme activity. (rcsb.org)
  • Precursor forms of IL-18 and IL-1β lack a signal peptide and they require cleavage by caspase-1 (IL-1β-converting enzyme) for their maturation, and hence for their biological activity ( 15 , 16 , 17 , 18 ). (jimmunol.org)
  • Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. (medsci.org)
  • These cleavages remove an -N[H.sub.2] peptide terminal and separate the small and large domains of the pro-enzyme so that it produces the mature hetero tetrameric caspases containing two large and two small domains. (thefreelibrary.com)
  • Enzyme kinetics assay shows that LS498 is readily cleaved by caspase-3, with excellent enzyme kinetic parameters k cat and K M of 0.55±0.01 s -1 and 1.12±0.06 μM, respectively. (spiedigitallibrary.org)
  • Caspase-14 is weakly processed into p18 and p11 subunits by caspase-8. (gentaur.com)
  • Caspases are a kind of cysteine proteinase consisting of a prodomain plus large and small catalytic subunits, that play a central role in cell apoptosis. (sinobiological.com)
  • In addition, caspases cleave the proenzyme precursors to produce the active subunits of caspases themselves ( 8 ). (sciencemag.org)
  • It is also known as caspase activated nuclease (CPAN), dna fragmentation factor 40 (DFF-40), DFF2 and DFFB. (wikipedia.org)
  • Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
  • Diosmin did not inhibit GBM95 and GBM02 cell proliferation, but it caused DNA fragmentation, as verified by the TUNEL assay, and increased cleaved caspase-3 expression in these cells. (scielo.br)
  • Caspase-dependent and -independent DNA fragmentation in Sertoli and germ cells from men with primary testicular failure: relationship with histological diagnosis," Human Reproduction , vol. 19, no. 2, pp. 254-261, 2004. (hindawi.com)
  • Twenty years ago, Newmeyer and colleagues first showed that the X. laevis egg extract, when incubated at room temperature, reconstituted the key molecular events of cellular apoptosis including cytochrome c release, nuclear condensation, internucleosomal fragmentation, and caspase activation. (springer.com)
  • This killing process was not accompanied by the activation of caspases or DNA fragmentation. (pubmedcentralcanada.ca)
  • This killing process proceeded without caspase activation, and was accompanied neither by apoptotic morphological changes of the cells nor by DNA fragmentation. (pubmedcentralcanada.ca)
  • Mere impairment of filaggrin (zeige FLG ELISA Kits ) degradation by loss of caspase 14 does not influence the inflammatory threshold of atopic dermatitis. (antikoerper-online.de)
  • Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. (wikipedia.org)
  • [5] Caspases involved with processing inflammatory signals are also implicated in disease. (wikipedia.org)
  • The function of caspase 4 is not fully known, but it is believed to be an inflammatory caspase, along with caspase 1, caspase 5 (and the murine homolog caspase 11), with a role in the immune system. (wikipedia.org)
  • Minocycline represses diabetes-induced inflammatory cytokine production, reduces the release of cytotoxins from activated microglia, and significantly reduces measurable caspase-3 activity within the retina. (diabetesjournals.org)
  • This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. (wikipedia.org)
  • Our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (DAP), a major ingredient of a TCM herb called Andrographis paniculata, shows anti-IAV activity that is mainly effective against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), and A/PR/8/34 (H1N1) in vitro and in vivo. (physiciansweekly.com)
  • Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. (nature.com)
  • In vitro , Anthrax lethal toxin strongly potentiated IL-1β secretion, and that response was NOD2 and caspase-1-dependent. (pnas.org)
  • The effects of a single dose of the alkylating agent cyclophosphamide (CPA or 4-hydroperoxycyclophosphamide), or the mechanism-based small molecule SMAC mimetic birinapant on caspase-3 activation was assessed in vitro and by [ 18 F]ICMT-11-PET in mice bearing 38C13 B-cell lymphoma, HCT116 colon carcinoma, or MDA-MB-231 breast adenocarcinoma tumors. (aacrjournals.org)
  • We confirmed that position 16, which associated with the N-terminal caspase cleavage of the NP, is important for optimal virus fitness in vitro and in vivo. (deepdyve.com)
  • The loop domain of Bcl-2 is cleaved at Asp 34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. (sciencemag.org)
  • In vitro translated human Bcl-2 was digested with purified recombinant caspase-3 (CPP32). (sciencemag.org)
  • Bcl-2 is cleaved by caspases both in vitro and in intact cells. (sciencemag.org)
  • A ) 35 S-labeled in vitro translated Bcl-2 and the indicated Bcl-2 mutants were digested with purified recombinant caspase-3 and analyzed on 12% SDS-polyacrylamide gels ( 24 ). (sciencemag.org)
  • Caspase-3 mRNA levels, estimated by semiquantitative RT-PCR, were elevated fivefold in ipsilateral cortex and twofold in hippocampus by 24 hr after TBI. (jneurosci.org)
  • Caspase-1 mRNA content also was increased after trauma, but to a lesser extent in cortex. (jneurosci.org)
  • To better understand mechanisms by which diabetes may modulate the apoptotic process, mRNA profiling of genes that directly or indirectly affect apoptosis was undertaken, as were measurements of diabetes-enhanced caspase activity. (diabetesjournals.org)
  • In addition, THC treatment of splenocytes resulted in a decrease of Bcl-2 mRNA and protein as measured by Northern and Western blotting, respectively, and the drug induced apoptosis was blocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-aspartic acid aldehyde. (biomedsearch.com)
  • Jung, Choi, Lee, Kim, Hwang, Choi: Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis. (antikoerper-online.de)
  • Expression of caspase-14 may protect from psoriasis and irradiation damage. (gentaur.com)
  • To identify the caspases expressed in normal human epidermis and to define their pattern of expression and activation. (ovid.com)
  • This study, the first exhaustive description of caspase expression and processing in normal human epidermis, indicates that in vivo granular keratinocytes express nine procaspases, and in addition the activated form of caspase-14. (ovid.com)
  • Unlike the other short prodomain caspases(caspase-3, caspase-6, and caspase-7), Caspase 14 was not processed by multiple death stimuli including activation of members of the tumor necrosis factor receptor family and expression of proapaptotic members of the bcl-2 family. (sinobiological.com)
  • The expression levels of caspases in tumors are found to be distinct from levels in normal tissue in a series of cancers. (aacrjournals.org)
  • For example, expression of caspase-3 was observed to be down-regulated in pediatric neuroblastoma ( 17 ), breast cancer ( 18 ), and gastric carcinoma ( 19 ), whereas caspase-7 was found to be down-regulated in colonic carcinoma ( 20 ), breast cancer ( 21 ), and gastric cancer ( 22 ). (aacrjournals.org)
  • Decreased expression of caspase-8 was also reported in neuroblastoma ( 23 ) and pediatric tumors ( 24 ). (aacrjournals.org)
  • Genetic polymorphisms in the caspase genes may affect cancer risk through altering expression levels and functions of these genes. (aacrjournals.org)
  • Thus, diabetes-enhanced apoptosis represents an important mechanism through which healing is impaired, and this can be explained, in part, by diabetes-increased expression of proapoptotic genes and caspase activity. (diabetesjournals.org)
  • Furthermore, a reduction of caspase-4 expression by small interfering RNA decreases ER stress-induced apoptosis in some cell lines, but not other ER stress-independent apoptosis. (rupress.org)
  • The results were reversed by the transfection of an exogenous caspase-9 expression vector. (spandidos-publications.com)
  • Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment. (spandidos-publications.com)
  • To document systematically where and when cells survive caspase-3 activation in vivo, we designed a system, CasExpress, which drives fluorescent protein expression, transiently or permanently, in cells that survive caspase-3 activation in Drosophila. (elifesciences.org)
  • Although inefficient, treatment with active caspase-3 produced a 23-kD proteolytic fragment of Bcl-2 (Fig. 1 A). However, a mutant of Bcl-2 ( 9 ) that lacks the loop domain (amino acids 32 to 80) was not susceptible to proteolysis, which suggested that the caspase cleavage site is localized within the loop. (sciencemag.org)
  • Caspase 14 possesses an unusually short prodomain and is highly expressed in embryonic tissues but absent from most of the adult tissues except for the skin, which suggests a role in ontogenesis and skin physiology. (sinobiological.com)
  • Cleavage of the procaspase at the specific Asp-X bonds leads to the formation of the mature caspase, which comprises the heterotetramer p20 2 -p10 2 , and the release of the prodomain. (jci.org)
  • The intersubunit disulfide bridge stabilizes the dimeric form of caspase-2, whereas all other long prodomain caspases exist as monomers in solution, and dimer formation is driven by ligand binding. (nih.gov)
  • A CARD motif has been identified in caspase-1, -2, and -9, and caspase-8 contains a long prodomain that may exert a similar regulatory function. (rupress.org)
  • Cisplatin also induced cleavage of caspase-9 and caspase-3, a process blocked by XIAP overexpression. (aacrjournals.org)
  • Cleavage of caspase-4 is not affected by overexpression of Bcl-2, which prevents signal transduction on the mitochondria, suggesting that caspase-4 is primarily activated in ER stress-induced apoptosis. (rupress.org)
  • Overexpression of Bcl-2 prevented caspase activation, the caspase cleavage of tau and improved place recognition memory in 3xTg-AD mice [ 8 ]. (pubmedcentralcanada.ca)
  • However, direct demonstration that APP is cleaved by caspases and is prevented following overexpression of Bcl-2 was not investigated. (pubmedcentralcanada.ca)
  • 6 ], we now demonstrate caspase-cleavage of APP does occur in 3xTgAD mice and is prevented along with the formation of extracellular deposits of Aβ following overexpression of Bcl-2. (pubmedcentralcanada.ca)
  • There are enzymes called executioner caspases that help cells to die in a carefully controlled process called apoptosis. (elifesciences.org)
  • Although the activation of executioner caspases generally leads to apoptosis, there are some circumstances in which cells are able to survive. (elifesciences.org)
  • Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. (nature.com)
  • The mechanism by which caspase-1 is activated to induce processing of pro-IL-1β and related cytokines is not well understood. (pnas.org)
  • We utilized phylogenetic, structural, and biophysical studies to define the interaction networks that facilitate the allosteric mechanism in caspase-3. (rcsb.org)
  • We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [ 18 F]ICMT-11 and positron emission tomography (PET). (aacrjournals.org)
  • The major mechanism of cell death is ROS-driven caspase-dependent apoptosis. (aacrjournals.org)
  • As of 2009, there are 11 or 12 confirmed caspases in humans [note 1] and 10 in mice, carrying out a variety of cellular functions. (wikipedia.org)
  • Activation of Caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues . (wikipedia.org)
  • However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x L , and Bid, which are potent inducers of apoptosis, the cleavage product of γHV68 Bcl-2 lacked proapoptotic activity. (asm.org)
  • The function of cellular Bcl-2 family members is regulated in part by caspases. (asm.org)
  • Caspases target multiple aspects of the cellular architecture to induce collapse of organelles and the cytoskeleton. (els.net)
  • Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases. (els.net)
  • Caspase-14 -deficient mice are more prone to the development of parakeratosis. (antikoerper-online.de)
  • Now, Zhao and colleagues report that a product resulting from caspase-2 cleavage of tau resists fibrillation, promotes synaptic dysfunction, and results in neurodegeneration in mice. (sciencemag.org)
  • The investigators showed that caspase-2 cleavage of tau at Asp314 resulted in a truncation product, ∆tau314, which was present at higher levels in the brains of AD mice compared with wild-type control animals. (sciencemag.org)
  • The memory impairments in these mice could be reversed by infusion of anti-caspase-2 morpholino oligonucleotides into the lateral ventricles of the mouse brain for 28 days. (sciencemag.org)
  • The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. (frontiersin.org)
  • Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. (frontiersin.org)
  • To determine a direct role for the caspase-cleavage of APP in 3xTg-AD mice, we designed a site-directed caspasecleavage antibody to APP and demonstrated it is a specific marker for caspase-cleaved APP. (pubmedcentralcanada.ca)
  • demonstrated that deleting the C-terminal caspase-cleavage consensus site within APP reversed the pathology and behavioral deficits associated with human APP transgenic mice [ 6 ]. (pubmedcentralcanada.ca)
  • the authors used in vivo imaging in rTg4510 mice, a reversible mouse model of tauopathy, to demonstrate the activation of caspases within tangle-bearing neurons [ 7 ]. (pubmedcentralcanada.ca)
  • The goal of the present study was examine directly a role for caspasemediated cleavage of APP in 3xTg-AD mice utilizing a novel site-directed caspase-cleavage antibody to APP. (pubmedcentralcanada.ca)
  • Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A et al (1998) Defects in regulation of apoptosis in caspase-2-deficient mice. (springer.com)
  • The Proteolysis Map Caspase Martinon F, Tschopp J (2007). (wikipedia.org)
  • Overall, our work demonstrates a role for phosphorylation in controlling caspase-mediated cleavage and shows that N-terminomic strategies can be tailored to study cross-talk between phosphorylation and proteolysis. (mcponline.org)
  • Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death. (jneurosci.org)
  • This enhanced caspase-8 oligomerization and activation are promoted through its interaction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light chain 3 (LC3), which are enriched at intracellular membranes in response to proteotoxic stress. (asm.org)
  • Since caspase-1 is known to cleave proIL-1β and proIL-18 into their mature, active forms, we analyzed the effect of a specific caspase-1 inhibitor on virus-induced IL-1β and IL-18 production. (jimmunol.org)
  • Insertion of the "human-like" G 16 →D mutation into avian NP, which resulted in susceptibility to caspase cleavage, did not rescue virulence, but made the reassortant virus even more attenuated. (deepdyve.com)
  • Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus. (wikipedia.org)
  • Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis . (wikipedia.org)
  • [5] Conversely, over-activation of some caspases such as caspase -3 can lead to excessive programmed cell death. (wikipedia.org)
  • Most caspases play a role in programmed cell death. (wikipedia.org)
  • Numerous studies have been performed to find novel agents (especial from natural plant) which can trigger programmed cell death (apoptosis) in tumor cells and hopefully to provide a new therapeutic approach for anticancer design ( 12 - 14 ). (spandidos-publications.com)
  • ARC is originally identified to be a caspase-inhibiting protein and can specifically inhibit the activation of caspase-2 and caspase-8, thereby blocking apoptosis induced by a variety of stimuli requiring the engagement of these caspases ( 1 ). (aacrjournals.org)
  • 15 Different death stimuli may activate different caspases. (ahajournals.org)
  • Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. (spandidos-publications.com)
  • Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. (spandidos-publications.com)
  • XIAP down-regulation induced Akt cleavage and apoptosis, and treatment of whole cell lysate with human recombinant active caspase-3 resulted in a similar pattern of Akt cleavage. (aacrjournals.org)
  • human caspase-3 recombinant protein. (abcam.com)
  • Alternatively, Jurkat cell lysates were digested for 4 hours with recombinant caspase-3. (sciencemag.org)
  • Freeze thaw will destroy a percentage in every cycle and should be avoided.Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. (gentaur.com)
  • We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. (nature.com)
  • [5] The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. (wikipedia.org)
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
  • However, it remains largely unknown how apparently disparate events implicated in apoptosis, such as oxidative stress, ionic dysregulation, and activation of mitogen-activated protein kinases (MAPK) and caspases, signal among one another to initiate and propagate cell death. (jneurosci.org)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Caspase-2-dependent cell death is important and evidenced in models of RGC degeneration. (arvojournals.org)
  • Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death. (sciencemag.org)
  • Both biochemical and genetic evidence indicates that Bcl-2 family members can regulate cell death induced by caspases ( 2 ). (sciencemag.org)
  • Induction of S phase cell arrest and caspase activation by polysaccharide peptide isolated from Coriolus versicolor enhanced the cell cycle dependent activity and apoptotic cell death of doxorubicin and etoposide, but not cytarabine in HL-60 cells. (greenmedinfo.com)
  • However, it has become clear that specific caspases also have functions independent of cell death. (biologists.org)
  • 1998) Identification of a new caspase homologue: caspase-14. (sinobiological.com)
  • Essential contribution of caspase 3/CPPp32 to apoptosis and its associated nuclear changes," Genes and Development , vol. 12, no. 6, pp. 806-819, 1998. (hindawi.com)
  • Kuwana T, Smith JJ, Muzio M, Dixit V, Newmeyer DD, Kornbluth S (1998) Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. (springer.com)
  • Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. (springer.com)
  • Synthetic peptide corresponding to Human Caspase-14 (N terminal). (abcam.com)
  • Phosphorylation of caspase-3 at a conserved allosteric site by p38-MAPK (mitogen-activated protein kinase) promotes survival in human neutrophils, and the modification of the loop is thought to be a key regulator in many developmental processes. (rcsb.org)
  • It has been shown to inhibit activator protein 1, a key transcription factor in inflammation and carcinogenesis, in human cell lines ( 13 ) and has been shown to possess antitumor properties and effectively inhibit cyclooxygenase-2 transcriptional activity in human colon cancer cells ( 14 , 15 ). (aacrjournals.org)
  • Synthetic peptide corresponding to Human Caspase-3 aa 150-250 (internal sequence) conjugated to keyhole limpet haemocyanin. (abcam.com)
  • We found that human caspase-4, a member of caspase-1 subfamily that includes caspase-12, is localized to the ER membrane, and is cleaved when cells are treated with ER stress-inducing reagents, but not with other apoptotic reagents. (rupress.org)
  • In this study, we investigated the function of p38 mitogen-activated protein kinase (MAPK) and caspase-8 in DATS-induced apoptosis of human CNE2 cells using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry assay, and Western blotting. (scielo.br)
  • In conclusion, our data indicate that p38MAPK and caspase-8 are involved in the process of DATS-induced apoptosis in human CNE2 cells and interact with each other. (scielo.br)
  • There are 14 caspases found in human [6]. (thefreelibrary.com)
  • Here, we describe a human Jurkat-derived cell line (JB-6) that is deficient in caspase 8. (pubmedcentralcanada.ca)
  • Meanwhile, chondrocytes apoptosis induced by NE can be alleviated by caspase inhibitor, zVAD-FMK and antioxidants, GSH. (frontiersin.org)
  • Furthermore, apoptosis induced by these fragments is blocked by the baculovirus caspase inhibitor P35, suggesting that these fragments kill cells in a caspase-dependent manner. (asm.org)