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
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.

p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. (1/311)

The cyclin-dependent kinase inhibitor p27Kip1 has been implicated as a drug resistance factor in tumor cells grown as spheroids or confluent monolayers. Here, we show that p27Kip1 overexpression also induces resistance to drug-induced apoptosis and cytotoxicity in human leukemic cells growing in suspension. The anti-apoptotic effect of p27Kip1 is not restricted to DNA-damaging agents but extends to the tubulin poison vinblastin, agonistic anti-Fas antibodies and macromolecule synthesis inhibitors. To further identify at which level this protein interferes with the cell death pathway, we investigated its influence on caspase activation and mitochondrial changes. Exposure of mock-transfected U937 cells to 50 microm etoposide activates procaspase-3 and the long isoform of procaspase-2 and induces mitochondrial potential decrease and cytochrome c release from mitochondria to the cytosol. All these events are prevented by p27Kip1 overexpression. p27Kip1 does not modulate Bcl-2, Bcl-X(L), Mcl-1 and Bax protein level in leukemic cells but suppresses Mcl-1 expression decrease observed in mock-transfected U937 cells undergoing etoposide-induced cell death. We conclude that p27Kip1 prevents cell death upstream of the final pathway common to many apoptotic stimuli that involves cytochrome c release from mitochondria and activation of downstream caspases.  (+info)

Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. (2/311)

Apoptosis is accompanied by the activation of a number of apoptotic proteases (caspases) which selectively cleave specific cellular substrates. Caspases themselves are zymogens which are activated by proteolysis. It is widely believed that 'initiator' caspases are recruited to and activated within apoptotic signalling complexes, and then cleave and activate downstream 'effector' caspases. While activation of the effector caspase, caspase-3, has indeed been observed as distal to activation of several different initiator caspases, evidence for a further downstream proteolytic cascade is limited. In particular, there is little evidence that cellular levels of caspase-3 that are activated via one pathway are sufficient to cleave and activate other initiator caspases. To address this issue, the ability of caspase-3, activated upon addition to cytosolic extracts of cytochrome c, to cause cleavage of caspase-2 was investigated. It was demonstrated that cleavage of caspase-2 follows, and is dependent upon, activation of caspase-3. Moreover, the activation of both caspases was inhibited by Bcl-2. Together, these data indicate that Bcl-2 can protect cells from apoptosis by acting at a point downstream from release of mitochondrial cytochrome c, thereby preventing a caspase-3 dependent proteolytic cascade.  (+info)

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (3/311)

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.  (+info)

CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. (4/311)

We have identified and characterized CIPER, a novel protein containing a caspase recruitment domain (CARD) in its N terminus and a C-terminal region rich in serine and threonine residues. The CARD of CIPER showed striking similarity to E10, a product of the equine herpesvirus-2. CIPER formed homodimers via its CARD and interacted with viral E10 but not with several apoptosis regulators containing CARDs including ARC, RAIDD, RICK, caspase-2, caspase-9, or Apaf-1. Expression of CIPER induced NF-kappaB activation, which was inhibited by dominant-negative NIK and a nonphosphorylable IkappaB-alpha mutant but not by dominant-negative RIP. Mutational analysis revealed that the N-terminal region of CIPER containing the CARD was sufficient and necessary for NF-kappaB-inducing activity. Point mutations in highly conserved residues in the CARD of CIPER disrupted the ability of CIPER to activate NF-kappaB and to form homodimers, indicating that the CARD is essential for NF-kappaB activation and dimerization. We propose that CIPER acts in a NIK-dependent pathway of NF-kappaB activation.  (+info)

DRONC, an ecdysone-inducible Drosophila caspase. (5/311)

Caspases play an essential role in the execution of programmed cell death in metazoans. Although 14 caspases are known in mammals, only a few have been described in other organisms. Here we describe the identification and characterization of a Drosophila caspase, DRONC, that contains an amino terminal caspase recruitment domain. Ectopic expression of DRONC in cultured cells resulted in apoptosis, which was inhibited by the caspase inhibitors p35 and MIHA. DRONC exhibited a substrate specificity similar to mammalian caspase-2. DRONC is ubiquitously expressed in Drosophila embryos during early stages of development. In late third instar larvae, dronc mRNA is dramatically up-regulated in salivary glands and midgut before histolysis of these tissues. Exposure of salivary glands and midgut isolated from second instar larvae to ecdysone resulted in a massive increase in dronc mRNA levels. These results suggest that DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis.  (+info)

Analysis of apoptosis and expression of bcl-2 gene family members in the human and baboon ovary. (6/311)

Recent data support a role for apoptosis, under tight regulatory control by bcl-2, oxidative stress response, tumor suppressor, and CASP gene family members, in mediating granulosa cell demise during follicular atresia in the rodent and avian ovary. Herein we evaluated the occurrence of apoptosis in the human and baboon ovary relative to follicular health status, and analyzed expression of several cell death genes in these tissues. In situlocalization of DNA strand breaks in fixed human and baboon ovarian tissue sections indicated that apoptosis was essentially restricted to granulosa cells of atretic antral follicles. Biochemical analysis of DNA oligonucleosomes in individual follicles isolated from baboon ovaries during the ovulatory phase revealed the presence of apoptotic DNA fragments in subordinate but not dominant follicles, thus substantiating the in situ labeling studies. Messenger RNA transcripts encoded by the bax death susceptibility gene, the bcl-xlong survival gene, the bcl-xshort pro-apoptosis gene, the p53 tumor suppressor gene, and two members of the CASP gene family (CASP-2/Ich-1, CASP-3/CPP32), were detected by Northern blot analysis of total RNA prepared either from human ovaries or from Percoll-purified granulosa-lutein cells obtained from patients undergoing assisted reproductive technologies. Lastly, immunohistochemical localization of the BAX death-susceptibility protein in the human ovary revealed abundant expression in granulosa cells of early atretic follicles, whereas BAX protein was extremely low or non-detectable in healthy or grossly-atretic follicles. We conclude that apoptosis occurs during, and is probably responsible for, folicular atresia in the human and baboon ovary. Moreover, apoptosis in the human ovary is likely controlled by altered expression of the same cohort of cell death regulatory factors recently implicated as primary determinants of apoptosis induction or suppression in the rodent ovary.  (+info)

Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia. (7/311)

In rats, striatal histotoxic hypoxic lesions produced by the mitochondrial toxin malonate resemble those of focal cerebral ischemia. Intrastriatal injections of malonate induced cleavage of caspase-2 beginning at 6 h, and caspase-3-like activity as identified by DEVD biotin affinity-labeling within 12 h. DEVD affinity-labeling was prevented and lesion volume reduced in transgenic mice overexpressing BCL-2 in neuronal cells. Intrastriatal injection of the tripeptide, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a caspase inhibitor, at 3 h, 6 h, or 9 h after malonate injections reduced the lesion volume produced by malonate. A combination of pretreatment with the NMDA antagonist, dizocilpine (MK-801), and delayed treatment with zVAD-fmk provided synergistic protection compared with either treatment alone and extended the therapeutic window for caspase inhibition to 12 h. Treatment with cycloheximide and zVAD-fmk, but not with MK-801, blocked the malonate-induced cleavage of caspase-2. NMDA injections alone resulted in a weak caspase-2 cleavage. These results suggest that malonate toxicity induces neuronal death by more than one pathway. They strongly implicate early excitotoxicity and delayed caspase activation in neuronal loss after focal ischemic lesions and offer a new strategy for the treatment of stroke.  (+info)

Role of caspases and possible involvement of retinoblastoma protein during TGFbeta-mediated apoptosis of human B lymphocytes. (8/311)

In this study, we investigated the involvement of caspases in TGFbeta-induced apoptosis in human B cells. Our results show that TGFbeta-mediated nuclear fragmentation, observed in the Epstein-Barr virus-negative Burkitt's Lymphoma cell line BL41, was abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Other apoptotic manifestations such as cell shrinkage, surface phosphatidylserine expression and chromatin condensation were strongly inhibited by zVAD-fmk but only partially by DEVD-fmk. This suggests that other caspases in addition to caspase-3 control these apoptotis-associated features. Specific activation of caspase-3 during TGFbeta-induced apoptosis was demonstrated by the DEVD-fmk-sensitive expression of the active p17 subunit of caspase-3 and by in vivo cleavage of PARP. In addition, TGFbeta treatment of BL41 promoted the expression of both dephosphorylated and truncated forms of the retinoblastoma protein. Inhibition of caspase-3 activity abolished both nuclear fragmentation and expression of the truncated retinoblastoma protein, without modifying the G1 cell cycle arrest induced by TGFbeta. Our data thus demonstrate that TGFbeta-induced apoptosis of lymphoma B lymphocytes is dependent on caspase activation and involves caspase-dependent cleavage of the retinoblastoma protein.  (+info)

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Book Apollon Hotel, Rust on TripAdvisor: See 49 traveler reviews, 273 candid photos, and great deals for Apollon Hotel, ranked #1 of 21 hotels in Rust and rated 4.5 of 5 at TripAdvisor.
Rabbit polyclonal BIRC6/APOLLON antibody. Validated in WB, IP, IHC and tested in Mouse, Human. Cited in 8 publication(s). Independently reviewed in 1 review(s). Immunogen corresponding to synthetic…
THE PUREST PROTEIN 50/50 Formula-X Protein BLEND FOR HARDCORE ATHLETES! Protein is the foundation of any athletes supplement regimen. For this reason, Apollon Nutrition created a pure blend with exactly 50% whey isolate and 50% micellar casein to create the ultimate fast/slow protein to use any time of the day. What ma
Looking for online definition of NEDD-3 in the Medical Dictionary? NEDD-3 explanation free. What is NEDD-3? Meaning of NEDD-3 medical term. What does NEDD-3 mean?
Caspase-4 (CASP-4, ICE(rel)-II, Protease ICH-2, Protease TX, CASP4, ICH2), C2087-23Y2 - Get the Best Quote/Price and read Reviews, Features and Research Applications
Clothos brain Apollon copies the purpose of Medulla in the human brain and the human hearts Sinoatrial Node and combines the features with the ability for interaction, programming, and functionality. The Apollon brain receives real-time signals from pressure, temperature, and displacement/Laser sensors. Apollon regulate by positive feedback control a set of proportional valves for the BpM, and the driving force and movement of the elastic Myocardium wall inside the Clio or Thalia SUPs.. The Apollon brain is a super compact PLC, which houses a 900 MHz quad-core ARM Cortex-A7 CPU and 16 GB Ram. A range of 15-bit high speed in/out analogue and digital channels corresponds with various sensors and actuators in real-time.. ...
Apollon on WN Network delivers the latest Videos and Editable pages for News & Events, including Entertainment, Music, Sports, Science and more, Sign up and share your playlists.
Susan Apollon Intuitive Psychologist, Psychotherapist, and Healer Susan Apollon is an intuitive psychologist, psychotherapist, and healer. For more than two…
Just as the Sun itself was perceived in the ancient world as the giver of light, Apollo as the representative of the Sun was perceived as the giver of inner light. Know thyself was the dictum carved in stone at his shrine at Delphi, and this emphasises the importance of Apollo as a symbol of consciousness.
Just as the Sun itself was perceived in the ancient world as the giver of light, Apollo as the representative of the Sun was perceived as the giver of inner light. Know thyself was the dictum carved in stone at his shrine at Delphi, and this emphasises the importance of Apollo as a symbol of consciousness.
09:39, 30 April 2015 Homo sapiens:Apoptosis Modulation and Signaling‎ (Corrected ID for AIFM1,CASP4,CASP2,CASP1,HSPA1A,PIDD,TP53,PRKD1,NAIP,XIAP,AIFM2,RIPK1 and PEA15 genes) ...
Use and dose of Nolvadex. To treat breast cancer, patients are recommended to take a tablet of Nolvadex 20 mg 1-2 times per day. If the side effects are absent, a one-time dose of Nolvadex may be increased up to 40 mg.. To treat cancer of kidneys or endometrium, patients are also prescribed a tablet of Nolvadex 20-30 mg 1-2 times per day.. A therapeutic effect is kept only during the prolonged treatment. The action of a tablet of Nolvadex 20 mg lasts for 12 to 20 hours, and therefore if you forgot to take a dose, there is an expectancy of the restored activity of the estrogenic receptors and a reduction of the treatment efficiency.. The treatment of tumors may take 1 to 5 years depending on the sensitivity to Nolvadex. In case of the prolonged treatment, a tolerance of Nolvadex may be developed. If a growth of the cancerous cells is restored during the medical study because of the use of Nolvadex, the treatment is terminated.. Recommendations for the use. ...
Obesity is associated with low-grade chronic inflammation without bacterial or viral infection, but the triggers and molecular mechanisms that lead to obesity-associated metabolic inflammation remain to be further explored. Although recent studies demonstrated palmitate triggered thioglycollate-elicited macrophage death under the stimulation of Gram-negative bacteria-derived LPS (39, 40), it did not explain the sterile inflammation associated with obesity, and it also raised concerns regarding physiology and activated status of these thioglycollate-activated macrophages (41). In this article, we report that when various dietary FAs were uptaken by stable macrophage cell lines or primary BMMs, only sFAs (e.g., PA, SA) were metabolized to produce Cers to induce macrophage cell death. Most importantly, we identified A-FABP as a new molecular sensor in mediating excess sFA-induced Cer production and in promoting macrophage cell death, thus contributing to the sterile chronic inflammation in ...
Apollon, also called Baculoviral IAP Repeat-Containing Protein 6 (BIRC6) or Baculoviral IAP Repeat-containing Ubiquitin Conjugating Enzyme (BRUCE), is an anti-apoptotic protein belonging to the IAP family, which consists of eight members. The genes of this family render cancer cells insensitive to apoptotic stimulation. The aim of the present study was to investigate and assess the role of small interference RNA (siRNA) in the regulation of Apollon gene expression in four different human cancerous cell lines; breast cancer (MCF-7), cervical cancer (HeLa), colon cancer (CaCo-2) and hepatocellular carcinoma (HepG-2). Lipofection was carried out to introduce the Apollon-specific siRNA into the cancerous cells and the Apollon expression levels were determined using RT-PCR. Trypan blue assay was conducted to assess the integrity of the cell membranes after being transfected. 3-(4, 5-dimethylthiazol-2-yl)-2-5- Diphenyl tetrazolium bromide (MTT) assay was also implemented to assess the cell viability ...
Caspase-3 plays a key role in initiation of cellular events during the apoptotic process. PromoKines Caspase-3 and Caspase-7 Immunoassay Kits allow quantification of the specific activity of caspase-3 and -7, respectively. Since caspase-3 and -7 share the same target substrate sequence (DEVD), it is difficult to differentiate the cleavage activity attributed by these two caspases in vitro. Thus, the assays utilize caspase-3 or -7 specific antibodies to capture the activated caspase-3 or -7 in cell lysate. Specific activity of caspase-3 or -7 can then be analyzed using the common caspase-3/7 substrate DEVD-AFC. The assay system ensures absolute specific detection of only caspase-3 or caspase-7 activity in apoptotic samples. Other caspases and non-specific proteases are not detected.. ...
CARD8 (caspase recruitment domain family, member 8), Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
Effects of ponicidin on the activity of caspase-3 in MKN28 cells. After treatment, the activity of caspase-3 in MKN28 cells was analyzed by the caspase-3 assay
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Neurodegenerative diseases pose one of the most pressing unmet medical needs today. It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently no disease-modifying therapies. Thus it is a potential target for neurodegenerative drug development. In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free structure shows caspase-6 in a partially mature but latent conformation. The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase ...
Carol Miletti has primary immune deficiency disorder (PIDD) and lives in Mound, Minnesota. She is very active in the PIDD community and the Immune Deficiency Foundation (IDF), and has become a vocal advocate for others who want to live life fully with PIDD. After a successful career in marketing and sales, she currently writes Carols Corner for BioTek reMEDys and actively participates in PIDD related organizations and educational conferences ...
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The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Get publications, patient education, and links to organizations and resources to help your PIDD patients receiving XEMBIFY (immune globulin subcutaneous human-klhw) 20%.
Salmonella induces programmed cell death in macrophages by complex mechanisms that involve distinct pathways and require the bacterial TTSS encoded in the pathogenicity island 1 (SPI-1 TTSS). One death pathway, which results in rapid macrophage death with features of necrosis, is dependent on caspase-1 and the SPI-1 TTSS-secreted protein SipB (Hersh et al., 1999; Brennan and Cookson, 2000; Jesenberger et al., 2000). However, macrophages from caspase-1−/− mice also undergo programmed cell death, although with delayed kinetics and different morphological features. Here, we have described another death pathway induced by Salmonella that is independent of caspase-1. A systematic bacterial genetic analysis led us to conclude that this cell death pathway is also dependent on SipB, a protein with membrane fusion activity that is delivered into host cells by the SPI-1 TTSS. This analysis was complicated by the known dual function of SipB, which acts both as an effector of virulence within cells and ...
AAAAI experts talk about what they would do if faced with a particular problem concerning allergies, asthma or primary immunodeficiency disease (PIDD).. Watch these videos to get tips on how to better manage your condition.. Read More. ...
Progression of the cell cycle and control of apoptosis are crucial and intimately linked processes that occur in all multicellular organisms during development, normal cellular differentiation and tissue homeostasis. Survivin (TIAP, BIRC5), a 16 kDa protein, is a member of the inhibitors of apoptosis (IAP)/BIRP gene family, which includes XIAP, c-IAP-1, c-IAP-2, ILP-2, NAIP, Livin and Apollon.
Hertz LD, Owzar K, Lessans S, Wing C, Jiang C, Kelly WK, Patel JN, Halabi S, Furukawa Y, Wheeler HE, Sibley A, Lassiter C, Weisman LS, Watson D, Krens SD, Mulkey F, Renn CN, Small EJ, Febbo PG, Shterev I, Kroetz D, Friedman PN, Mahoney JF, Carducci MA, Kelley MJ, Nakamura Y, Kubo M, Dorsey SG, Dolan ME, Morris MJ, Ratain MJ and McLeod HL. Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy. Clin Cancer Res. 2016 Oct 1. PMID: 27143689 ...
In order to implement search with assistance from the Android system (to deliver search queries to an activity and provide search suggestions), your application must provide a search configuration in the form of an XML file. This page describes the search…
This trial will test the use of a synthetic siRNA that blocks caspase 2, an important enzyme in the apoptosis cycle. In ... "Ocular neuroprotection by siRNA targeting caspase-2". Cell Death & Disease. 2 (6): e173. doi:10.1038/cddis.2011.54. PMC 3168996 ... 18 (2): 191-221. doi:10.1016/S1350-9462(98)00016-0. PMID 9932283. Hayreh SS, Zimmerman MB (July 2008). "Non-arteritic anterior ... 118 (2): 291-2. PMID 10676804. Pomeranz HD, Smith KH, Hart WM, Egan RA (March 2002). "Sildenafil-associated nonarteritic ...
But in contrast, the caspase-2, which is acetylated by NatA, can interact with the adaptor protein RIP associated Ich-1/Ced-3 ... This could activate caspase-2 and induce cell apoptosis. Ribosome proteins play an important role in the protein synthesis, ... 2 (6): 456-462. doi:10.1007/s13238-011-1063-9. PMC 3690542. PMID 21748595. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W (2008). " ... Table 2. Overview of the expression of NatA subunits in various cancer tissues Proteins are typically acetylated on lysine ...
Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its ... Through its CARD domain, this protein interacts with, and thus recruits, caspase 2/ICH1 to the cell death signal transduction ... Droin N, Beauchemin M, Solary E, Bertrand R (December 2000). "Identification of a caspase-2 isoform that behaves as an ... Droin N, Beauchemin M, Solary E, Bertrand R (2000). "Identification of a caspase-2 isoform that behaves as an endogenous ...
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 ... T cells from patient and normal control supported in culture for ,10 days with mitogen stimulation and IL-2 expansion and then ... 148 (2): 205-16. doi:10.1111/j.1365-2141.2009.07991.x. PMC 2929682 . PMID 19930184.. ...
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 ...
Bonfoco E, Li E, Kolbinger F, Cooper NR (August 2001). "Characterization of a novel proapoptotic caspase-2- and caspase-9- ... Proteomics-based identification of proapoptotic caspase adapter protein as a novel serum marker of non-small cell lung cancer ...
Qin W, Hu J, Guo M, Xu J, Li J, Yao G, Zhou X, Jiang H, Zhang P, Shen L, Wan D, Gu J (Aug 2003). "BNIPL-2, a novel homologue of ... 308 (2): 379-85. doi:10.1016/S0006-291X(03)01387-1. PMID 12901880. Xie L, Qin WX, He XH, Shu HQ, Yao GF, Wan DF, Gu JR (May ... Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein is a protein that in humans is encoded by the BNIPL gene. BNIPL ... Zhou YT, Soh UJ, Shang X, Guy GR, Low BC (Mar 2002). "The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a ...
Nicholson, D. & Thornberry, N.A. (2004). „Caspase-3 and caspase-7". Ур.: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7,, 3.4.21/22/23/24, ... Nicholson, D. & Thornberry, N.A. (2004). „Caspase-3 and caspase-7". Ур.: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. ... Chang, H.Y. & Yang, X. (2000). „Proteases for cell suicide: functions and regulation of caspases". Microbiol. Mol. Biol. Rev. ...
... in a mechanism regulated by caspase-2. She received the Basic Science Research Mentoring Award from the Duke School of Medicine ... "Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2". Cell. 123 (1): 89-103. doi ...
Recently, oocytes were used recently to study the biochemical mechanisms of caspase-2 activation; importantly, this mechanism ... "Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2". Developmental Cell. 16 ... 408 (2): 180-187. doi:10.1016/j.ydbio.2015.02.003. PMC 4684227. PMID 25704511. Gurdon, J. B.; Lane, C. D.; Woodland, H. R.; ... 35 (2): 145-149. doi:10.1016/j.devcel.2015.09.017. ISSN 1878-1551. PMID 26506304. Rana AA, Collart C, Gilchrist MJ, Smith JC ( ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... 3.0.CO;2-5. PMID 10508479. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than ... 18 (2): 676-84. doi:10.1128/mcb.18.2.676. PMC 108778. PMID 9447963. "Entrez Gene: SFRS2IP splicing factor, arginine/serine-rich ... the sensitivity of PS1 to caspases". FEBS Lett. 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/ ...
... prevents caspases from being activated. The caspases, a type of protease, remain inactive until signaled through a cascade to ... Bcl-2 is an important family of intracellular proteins that helps regulate apoptosis, or cell suicide. Bcl-2, paired with other ... Cory, Suzanne; Huang, David C. S.; Adams, Jerry M. (1 January 2003). "The Bcl-2 family: roles in cell survival and oncogenesis ... In particular, the oncoprotein Myc and the Bcl-2 protein family are of interest to her current research lab. ...
2007). "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway". EMBO J. 26 ( ... Tinel A, Tschopp J (2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic ... Vakifahmetoglu H, Olsson M, Orrenius S, Zhivotovsky B (2006). "Functional connection between p53 and caspase-2 is essential for ... and caspase 2. GRCh38: Ensembl release 89: ENSG00000177595 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000025507 ...
Fushimi K, Ray P, Kar A, Wang L, Sutherland LC, Wu JY (October 2008). "Up-regulation of the proapoptotic caspase 2 splicing ... 66 (2): 270-284.e13. doi:10.1016/j.molcel.2017.03.014. PMID 28431233. Jung JH, Lee H, Cao B, Liao P, Zeng SX, Lu H (January ... 2: 1885-90. doi:10.1100/tsw.2002.859. PMC 6009235. PMID 12920317. Oh JJ, Razfar A, Delgado I, Reed RA, Malkina A, Boctor B, ... 2 (4): 167-74, 199-210. doi:10.1093/dnares/2.4.167. PMID 8590280. Coleman MP, Ambrose HJ, Carrel L, Németh AH, Willard HF, ...
2000). "Caspase-2 Is Localized at the Golgi Complex and Cleaves Golgin-160 during Apoptosis". J. Cell Biol. 149 (3): 603-12. ... Maag RS, Mancini M, Rosen A, Machamer CE (Jun 2005). "Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory ... Sbodio JI, Hicks SW, Simon D, Machamer CE (2006). "GCP60 preferentially interacts with a caspase-generated golgin-160 fragment ...
... novel inducer of T cell apoptosis with distinct profile of caspase activation". Journal of Immunology. 173 (6): 3825-37. doi: ... Core 2 glycans terminate in galactose or sialic acid, whereas core 1 is branched and has potential for large carbohydrate ... 1572 (2-3): 263-73. doi:10.1016/S0304-4165(02)00313-6. PMID 12223274. Sturm A, Lensch M, André S, Kaltner H, Wiedenmann B, ... Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 ...
Conversion of Bcl-2 to a Bax-like death effector by caspases. 278:5345. Science. 1997 Andrea Ventura, David G Kirsch, Margaret ... His highest cited papers are "Conversion of Bcl-2 to a Bax-like death effector by caspases", at 1332 times, and "Restoration of ...
"Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent ... Hexokinase 2 also known as HK2 is an enzyme which in humans is encoded by the HK2 gene on chromosome 2. Hexokinases ... 31 (2): 197-212. doi:10.1016/s0047-6374(85)80030-0. PMID 4058069. S2CID 40877603. Wyatt, E; Wu, R; Rabeh, W; Park, HW; Ghanefar ... 99 (2): 260-6. doi:10.1111/j.1349-7006.2007.00683.x. PMID 18271924. S2CID 25720472. Overview of all the structural information ...
227 (1-2): 344-351. doi:10.1111/j.1432-1033.1995.tb20395.x. PMID 7851406. "Entrez Gene: PKN2 protein kinase N2". Koh H, Lee KH ... 41 (2): 561-9. doi:10.1021/bi010719z. PMID 11781095. Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (July ... 4 (2): 306-315. doi:10.1021/pr0498436. PMID 15822905. Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, ... 496 (2-3): 101-104. doi:10.1016/S0014-5793(01)02401-2. PMID 11356191. Hodgkinson CP, Sale GJ (2002). "Regulation of both PDK1 ...
... induces a caspase-independent autophagic cell death". Cell Death and Differentiation. 10 (7): 798-807. doi:10.1038/sj.cdd. ... 3.0.CO;2-P. PMID 10980529. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ... 46 (2): 215-9. doi:10.1093/rheumatology/kel205. PMID 16837472. Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, ... 34 (2-3): 95-107. doi:10.1016/j.mam.2012.12.009. PMC 3853582. PMID 23506860. Perland E, Lekholm E, Eriksson MM, Bagchi S, Arapi ...
Apoptosis involves the mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF), which activate caspase- ... 2011). Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor. Cell Death & Disease ... it is suggested that a Caspase inhibitor, TRP601, is a candidate for neuroprotective strategy in prenatal brain injury ... 38 (2): 742-745. doi:10.1161/01.STR.0000247921.97794.5e. PMID 17261729. Rutherford, MA; Ramenghi, LA; Cowan, FM (September 2012 ...
... been known to regulate apoptosis by regulating the phosphorylation status of apoptotic proteins such as caspase-3 and caspase-8 ... "Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2". ... 63 (2): 94-100. doi:10.1002/iub.427. PMC 4497508. PMID 21360638. Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, ... 7 (2): 265-267. doi:10.4161/cbt.7.2.5745. PMID 18347426. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris ...
1998). "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. ... "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. 17 (8): ... cIAP2 is a member of the inhibitor of apoptosis family that inhibit apoptosis by interfering with the activation of caspases. ... functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7". J. Biol. Chem. 275 (35 ...
Lee ZH, Lee SE, Kwack K, Yeo W, Lee TH, Bae SS, Suh PG, Kim HH (March 2001). "Caspase-mediated cleavage of TRAF3 in FasL- ... TRAF3 has been shown to interact with: CD27, CD40, Caspase 3 Lymphotoxin beta receptor, Nucleoporin 62, RANK, TANK, and TNFSF14 ... "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". The Journal of ... 3.0.CO;2-E. PMID 8761950. VanArsdale TL, VanArsdale SL, Force WR, Walter BN, Mosialos G, Kieff E, Reed JC, Ware CF (March 1997 ...
Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751- ... "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ... ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the ... 2 (3): 389-95. doi:10.1016/s1097-2765(00)80283-x. PMID 9774977. Hoeflich KP, Yeh WC, Yao Z, Mak TW, Woodgett JR (October 1999 ...
... has been shown to interact with: ALS2CR2, Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1 ... Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ...
Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751- ... Shu HB, Halpin DR, Goeddel DV (1997). "Casper is an FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751-63. ... TRAF1 has been shown to interact with: BIRC2, Baculoviral IAP repeat-containing protein 3, CFLAR, Caspase 8, HIVEP3, RANK ... "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ...
The T cell also produces IL-2, which directly influences B cells. As a result of this net stimulation, the B cell can undergo ... 67 (1): 2-17. doi:10.1002/jlb.67.1.2. PMID 10647992. S2CID 35592719. Schattner EJ (May 2000). "CD40 ligand in CLL pathogenesis ... Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (December 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors ... of specific caspases". The EMBO Journal. 16 (23): 6914-25. doi:10.1093/emboj/16.23.6914. PMC 1170295. PMID 9384571. Ishida TK, ...
... s are more similar to caspases than metacaspases are, indicating that this group of proteases diverged from caspases ... The Proteolysis Map MALT1 Caspase Metacaspase MALT lymphoma Uren A, O'Rourke K, Aravind L, Pisabarro M, Seshagiri S, Koonin E, ... It is currently unclear whether the paracaspases (and caspases) found in eukaryotes are a result from several (at least 2) ... Paracaspases are proteins related to caspases present in animals and slime mold, in contrast to metacaspases, which are present ...
FLIP then binds to caspase-8, forming a caspase-8 FLIP heterodimer in the cytosol that disrupts the activity of caspase-8 and ... This new complex contains the caspase-8 FLIP heterodimer as well as RIPK1 and RIPK3. Caspase inhibition within this complex ... The activation of caspase 3 and 9 by the apoptosome starts a proteolitic cascade that eventually leads to the degradation of ... Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (September 2000). "Activation of the NF-kappaB pathway by caspase 8 and ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 2 (8). doi:10.1101/cshperspect.a006239. PMC 3405821. PMID 22908189.. *^ Su DM, Zhang Q, Wang X, He P, Zhu YJ, Zhao J, Rennert ... 2 (1): 48-58. doi:10.1038/nrc706. PMID 11902585.. *^ Cho S, Lu M, He X, Ee PL, Bhat U, Schneider E, Miele L, Beck WT (December ... doi:10.1016/S0969-9961(03)00123-2. PMID 14572442.. *^ Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... ISBN 978-1-136-84407-2.. *^ a b Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). ... 3 (2): 243-54. PMID 10464676.. *. Martin J, et al. (2004). "The sequence and analysis of duplication-rich human chromosome 16 ... CMTM2: encoding protein CKLF-like MARVEL transmembrane domain-containing protein 2. *CCDC135: encoding protein Coiled-coil ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... 20 (2): 158-72. doi:10.1016/j.ccr.2011.07.011. PMID 21840482. Petersen, Sean L.; Wang, Lai; Yalcin-Chin, Asligul; Li, Lin; ... 14 (2): 115-22. doi:10.1016/j.semcancer.2003.09.016. PMID 15018895. Jechlinger, M.; Sommer, A; Moriggl, R; Seither, P; Kraut, N ... The cell then releases IL-2, which binds to its own new IL-2 receptors, causing self-stimulation and ultimately a monoclonal ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 10 (2): 104-115. doi:10.1038/nrm2630. PMID 19165213.. *^ Sakata E, Stengel F, Fukunaga K, Zhou M, Saeki Y, Förster F, ... 2 (3): 199-204. doi:10.1038/nsb0395-199. PMID 7773788.. *^ Inobe T, Fishbain S, Prakash S, Matouschek A (March 2011). "Defining ... 3 (2): 129-36. PMID 14985453.. *^ Zollner TM, Podda M, Pien C, Elliott PJ, Kaufmann R, Boehncke WH (March 2002). "Proteasome ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... 117 (2): 289-96. doi:10.1172/JCI30555. PMC 1783813. PMID 17273548.. *^ Tracey KJ (June 2009). "Reflex control of immunity". ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ...
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 ... 6 (2): 97-105. doi:10.1038/ncb1086. PMID 14743216.. *^ Micheau O, Tschopp J (July 2003). "Induction of TNF receptor I-mediated ... 13 (2): 225-234. doi:10.1002/ibd.20062. PMID 17206706.. *^ Kolb WP, Granger GA (1968). "Lymphocyte in vitro cytotoxicity: ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 66 (2): 227-34. doi:10.1002/ana.21620. PMID 19743466.. *^ a b c Yoo YE, Ko CP (September 2011). "Treatment with trichostatin A ... M (y) 2; H (ni) 3 M (y) 9; H (ny) D (y) 11 R (y) 17; H (ny) MC 23, 24; M (y) 25; H (v) 26, 27, 28, 29 ... 10 (2): 99-106. doi:10.1080/17482960802320487. PMID 18688762.. *^ a b Piepers S, Veldink JH, de Jong SW, van der Tweel I, van ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... Scheme 2 is the newer synthesis route which was designed to make the reaction more direct and to produce better yields. This ... 2 (1): 36. doi:10.1186/1756-8722-2-36. PMC 2736171 . PMID 19674465. Vacca A, Ribatti D, Roncali L, et al. (July 1994). "Bone ... In vitro data suggests this co-stimulation leads to increased Th1 type cytokine release of IFN-γ and IL-2 that further ...
88 (2): 595-603. PMID 12163512.. *^ Chou WH, Wang D, McMahon T, Qi ZH, Song M, Zhang C, Shokat KM, Messing RO (October 2010). " ... 16 (2): 477-83. doi:10.1017/S1461145712000685. PMC 3802523. PMID 22827965.. *^ Egan MF, Kojima M, Callicott JH, Goldberg TE, ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... 21 (2): 127-32. doi:10.1002/hipo.20775. PMID 20232397.. *^ Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (April ...
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 · ... Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · .23 MMP-7 · .24 MMP-2/MMP-5 · .35 MMP-9 · ... 1 ADH · .2 ALR · .54 LAD · .90 RAD · .91 RAD · .144 PAD · .194 CAD · .195 CAD ... 16 · .17 (.1 CPA · .2 CPB · .3 CPN · .4 CPS · .6 ACP · .9 CPS · .21 PSMA) · .18 ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... 264 (2): 457-64. doi:10.1006/bbrc.1999.1516. PMID 10529385.. *^ a b c Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta ... 117 (2): 473-81. doi:10.1172/JCI28971. PMC 1783820. PMID 17273559.. *^ Chen H, Li C, Huang J, Cung T, Seiss K, Beamon J, ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ...
"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- ... 272 (2): 1110-6. doi:10.1074/jbc.272.2.1110. PMID 8995410.. *^ a b c d e f g Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie ... 272 (2): 1101-9. doi:10.1074/jbc.272.2.1101. PMID 8995409.. *^ Méthot N, Song MS, Sonenberg N (October 1996). "A region rich in ... 83 (1-2): 74-5. doi:10.1159/000015130. PMID 9925932.. *. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D ( ...
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 ... 2] IPM에 의하여 망막색소상피 전구체가 망막색소상피세포로 성숙된다.[3] 해부학적 위치[편집]. 망막색소상피세포는 육각형 모양의 세포들이 단일층을 구성하고 있다. [4] 이 세포들은 색소 과립 (pigmented ... "DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration". 》PNAS》 111 (45): 16082 ... 기형종(Teratoma, 테라토마) : 인체 내의 3배엽 중에서 한 가지 배엽 이상의 세포가 발견되는 암을 의미함.(출처 : [[2]]) 혹은, 3배엽(외배엽, 내배엽, 중배엽) 유래의 세포나 조직이 관찰되는 종양을 의미한다.[ ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... 2] Cell death is relative to both the length of exposure to a harmful stimulus and the severity of the damage caused.[1] Cell ... but about 1-2% of damages involve both strands.[22] The double-strand damages include double-strand breaks (DSBs) and inter- ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... 1,0 1,1 1,2 1,3 1,4 Daneholt, Bertil. "Advanced Information: RNA interference". The Nobel Prize in Physiology or Medicine 2006 ... 52,0 52,1 52,2 Saumet A, Lecellier CH (2006). "Anti-viral RNA silencing: do we look like plants?". Retrovirology 3 (3): 3. PMC ... "PLoS Genet 2 (7): e108. PMC 1500810. PMID 16839188. doi:10.1371/journal.pgen.0020108. Arquivado dende o orixinal o 22 de ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... 2008;(2):CD005592. doi:10.1002/14651858.CD005592.pub2. PMID 18425924. *^ a b c d American Psychiatric Association practice ... 2003;6(2):315-20. doi:10.1089/109662103764978641. PMID 12854952. *^ a b c Survival and Cause of Death in Alzheimer's Disease ... 2012;368(2):107-16. doi:10.1056/NEJMoa1211103. PMID 23150908. *^ TREM2 variants in Alzheimer's disease. The New England Journal ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... Cysteine (symbol Cys or C;[3] /ˈsɪstiiːn/)[4] is a semiessential[5] proteinogenic amino acid with the formula HO2CCH(NH2)CH2SH ... 4 (2): 125-30. doi:10.1007/BF01966822. PMID 4842541.. *^ Kanter MZ (October 2006). "Comparison of oral and i.v. acetylcysteine ... 202 (2): 138-48. doi:10.1007/s004250050112. PMID 9202491.. *^ Bulaj G, Kortemme T, Goldenberg DP (June 1998). "Ionization- ...
... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... along the caspase-9, caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases. Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ... 17 (2): 259-72. doi:10.1210/me.2002-0120. PMID 12554753.. *. Anisfeld AM, Kast-Woelbern HR, Meyer ME, Jones SA, Zhang Y, ... negative regulation of interleukin-2 production. • positive regulation of insulin secretion involved in cellular response to ...
Expression of this gene is up-regulated by interleukin-2.[7]. References[edit]. *^ a b c GRCh38: Ensembl release 89: ... 259 (2): 401-7. doi:10.1006/bbrc.1999.0700. PMID 10362521.. *. Brown J, Matutes E, Singleton A, et al. (1998). "Lymphopain, a ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 120 (2): 257-69. doi:10.1093/brain/120.2.257. PMID 9117373.. *^ White, Tonya; Su, Shu; Schmidt, Marcus; Kao, Chiu-Yen; Sapiro, ... 7 (2): 136-44. doi:10.1038/nn1172. PMID 14703572.. *^ Rakic, P (May 1972). "Mode of cell migration to the superficial layers of ... 22 (2): 482-92. doi:10.1093/cercor/bhr312. PMID 22114081.. *^ Zilles, K; Armstrong, E; Moser, KH; Schleicher, A; Stephan, H ( ...
"N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases". Nature 457 (7232): 981-989. doi:10.1038/ ... doi:10.1016/S0140-6736(08)61075-2 . PMID 18640458 . *↑ Lacor PN,et al.; Buniel, MC; Furlow, PW; Clemente, AS; Velasco, PT; Wood ... doi:10.1016/S0166-2236(00)02031-2 . PMID 11801334 . *↑ Nistor M, Don M, Parekh M, et al. (Oktoba 2007). "Alpha- and beta- ... Trans. 33 (Pt 2): 335-8. doi:10.1042/BST0330335 . PMID 15787600 . *↑ Ohnishi S, Takano K (Machi 2004). "Amyloid fibrils from ...
"Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death". Journal of ... 7 (2): 106-19. doi:10.1634/theoncologist.7-2-106. PMID 11961194.. (Flanagan et al. 1955 in Mullen & Tanabe 2002 ... IL-2).[21] An NDV/F3aa-IL-2 strain induced the immune system, giving a cytotoxic effect on the tumor cells.[22] A 15-year study ... 2] Though there are rare cases where the disease gives a mild fever and/or conjunctivitis. Its effects are most notable in ...
Diaz F, Bourguignon LY (2000). «Selective down-regulation of IP(3)receptor subtypes by caspases and calpain during TNF alpha - ... ITPR2 (do inglês, inositol 1,4,5-triphosphate receptor, type 2) é uma proteína que é codificado pelo gene humano ITPR2.[1] A ... 183 (2): 297-311. PMC 2568025. . PMID 18936250. doi:10.1083/jcb.200803172. !CS1 manut: Uso explícito de et al. (link) !CS1 ... 2 (1): 9-22. PMID 8081734. !CS1 manut: Uso explícito de et al. (link) !CS1 manut: Nomes múltiplos: lista de autores (link) ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... 19 (1-2): 73-7. PMID 16178278.. *. Bucur O, Ray S, Bucur MC, Almasan A (May 2006). "APO2 ligand/tumor necrosis factor-related ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
... suggest that mitochondrial failure is caused by immune-mediated destabilization of mitochondria as part of a TNF-alpha/caspase- ... Vitamin D deficiency and oxidative stress are 2 examples.) Kekki1978 (talk) 12:51, 25 September 2018 (UTC). The CDC stated that ... The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis′[2] ... Threads older than 2 months may be archived by Lowercase sigmabot III. ...
... accompanied by activations of nuclear factor kappaB and caspase-3.. „Life Sci". 77 (7), s. 824-836, 2005-07-01. PMID: 15936354. ... Phytohemistry". 41 (2), s. 433-438, 1996. *↑ Pino, J.A., Marquez, E., Castro, D.. Volatile and nono-volatile acids of noni ( ... Clinical and Experimental Dermatology". 23 (2), s. 56-8, 1998. DOI: 10.1046/j.1365-2230.1998.00315.x. PMID: 9692305. ... 2]. Został szeroko rozprzestrzeniony jako przyprawa i środek leczniczy. Występuje w efekcie także w Afryce, Ameryce Północnej ( ...
Caspase Substrates. *Cathepsin Substrates. *Chymotrypsin Substrates. *Dipeptidyl Peptidase (DPP) Subtrates. *Elastase ... FastPrep-24 5G™ FastPrep-96™ SuperFastPrep-2™ Personal Homogenizer FastPrep® Adapters Lysing Compositions & Tubes. FastPrep® ...
Caspase Substrates. *Cathepsin Substrates. *Chymotrypsin Substrates. *Dipeptidyl Peptidase (DPP) Subtrates. *Elastase ... FastPrep-24 5G™ FastPrep-96™ SuperFastPrep-2™ Personal Homogenizer FastPrep® Adapters Lysing Compositions & Tubes. FastPrep® ...
Caspase Substrates. *Cathepsin Substrates. *Chymotrypsin Substrates. *Dipeptidyl Peptidase (DPP) Subtrates. *Elastase ... FastPrep-24 5G™ FastPrep-96™ SuperFastPrep-2™ Personal Homogenizer FastPrep® Adapters Lysing Compositions & Tubes. FastPrep® ...
Caspase Substrates. *Cathepsin Substrates. *Chymotrypsin Substrates. *Dipeptidyl Peptidase (DPP) Subtrates. *Elastase ... FastPrep-24 5G™ FastPrep-96™ SuperFastPrep-2™ Personal Homogenizer FastPrep® Adapters Lysing Compositions & Tubes. FastPrep® ...
Caspase Substrates. *Cathepsin Substrates. *Chymotrypsin Substrates. *Dipeptidyl Peptidase (DPP) Subtrates. *Elastase ... FastPrep-24 5G™ FastPrep-96™ SuperFastPrep-2™ Personal Homogenizer FastPrep® Adapters Lysing Compositions & Tubes. FastPrep® ...
  • This enzyme catalyses the following chemical reaction Strict requirement for an Asp residue at P1, with Asp316 being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp- Caspase-2 is an initiator caspase, as are caspase-8 (EC, caspase-9 (EC and caspase-10 (EC (wikipedia.org)
  • upon cleavage of the substrate by caspase 2 or related caspases, free AFC emits a yellow-green fluorescence (λmax = 505 nm), which can be quantified using a fluorometer or a fluorescence microtiter plate reader. (abcam.com)
  • In biochemical assays, caspase-2 uniquely prefers a pentapeptide (such as VDVAD) rather than a tetrapeptide, as required for efficient cleavage by other caspases. (rcsb.org)
  • 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 improvements in memory function corresponded to a reduction in ∆tau314, linking the tau caspase-2 cleavage product to neurodegenerative behavioral deficits in vivo. (sciencemag.org)
  • Caspase-2 cleavage of tau reversibly impairs memory. (sciencemag.org)
  • Preventing caspase-2 cleavage of tau blocks memory impairment in an animal model of Alzheimer's disease. (sciencemag.org)
  • 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)
  • 13 14 Caspase 2 is activated by cleavage into three fragments that are then further processed into 18- and 12-kD active subunits. (bloodjournal.org)
  • The carboxyl-terminal Bcl-2 cleavage product triggered cell death and accelerated Sindbis virus-induced apoptosis, which was dependent on the BH3 homology and transmembrane domains of Bcl-2. (sciencemag.org)
  • Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. (sciencemag.org)
  • Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus-induced apoptosis. (sciencemag.org)
  • Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death. (sciencemag.org)
  • Cleavage of these proteins by caspases may either activate or inactivate essential functions or produce cleavage products with altered activities. (sciencemag.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)
  • Two potential caspase cleavage sites occur within the loop at positions 34 and 64. (sciencemag.org)
  • The P4 position of caspase cleavage sites confers protease specificity ( 10 ). (sciencemag.org)
  • Incubation of both OCIM2 and K562 cells with WP1066 activated caspase-3, induced cleavage of poly(ADP-ribose) polymerase, and caused caspase-dependent apoptotic cell death. (aacrjournals.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)
  • These cleavages are likely to be physiologically significant, as mutation of the cleavage sites in Bcl-2 and Bcl-x L enhances their antiapoptotic activities ( 8 , 13 ). (asm.org)
  • The caspase cleavage products of Bcl-2 and Bcl-x L are potently proapoptotic, based on transfection studies expressing protein fragments that are equivalent to caspase cleavage products ( 8 , 13 ). (asm.org)
  • Bilateral ballistic closed globe blunt ocular trauma was induced in female Lister-hooded rats and caspase-2 cleavage and localization assessed by Western blotting and immunohistochemistry. (arvojournals.org)
  • Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2 -transfected PC12 cells. (aspetjournals.org)
  • In contrast, bcl-2 transfection protected PC12 cells from cisplatin-induced apoptosis, and cisplatin treatment did not result in Bcl-2 cleavage. (aspetjournals.org)
  • Similarly, Bcl-2 cleavage did not occur and Bcl-2-mediated protection from, rather than potentiation of apoptosis was observed after NCS treatment of MCF-7 breast cancer cells. (aspetjournals.org)
  • The caspase 3-specific inhibitor Ac-DEVD-CHO prevented Bcl-2 cleavage and attenuated NCS-induced apoptosis in bcl-2 -transfected PC12 cells, whereas it had no effect on NCS-induced apoptosis in mock-transfected PC12 cells. (aspetjournals.org)
  • Furthermore, MCF-7 cells do not express caspase 3, a finding in concert with the lack of Bcl-2 cleavage in this line. (aspetjournals.org)
  • Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis. (aspetjournals.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)
  • The caspase cleavage of APP as well as the formation of extracellular Aβ plaques was prevented in 3xTg-AD animals overexpressing Bcl-2. (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)
  • Overexpression of Bcl-2 prevented caspase activation, the caspase cleavage of tau and improved place recognition memory in 3xTg-AD mice [ 8 ]. (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)
  • 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)
  • During apoptosis pro-caspase-2 is processed at aspartate residues by self-proteolysis and/or cleavage by upstream caspases. (antibody-antibodies.com)
  • Silibinin increased p53 protein level together with its increased phosphorylation at serine 15, activated caspase cascade and caused Bid cleavage for apoptosis. (oup.com)
  • Interestingly, silibinin-induced apoptosis was mediated, in part, via Cip1/p21 cleavage by caspase, which was reversed by Cip1/p21 siRNA. (oup.com)
  • Together, these results suggested the novel mechanisms for apoptosis induction by silibinin involving p53-caspase 2 activation and caspase-mediated cleavage of Cip1/p21. (oup.com)
  • Caspase 2 can carry out proteolytic cleavage of other proteins and it possesses a similar amino acid sequence to some of the initiator caspases such as caspase-1, caspase-4, caspase-5, and caspase-9. (elisakits.co.uk)
  • Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
  • Caspase-2 failed to induce cytochrome c release from mitochondria with Bid -/- background, and the release could be restored by addition of the wild-type Bid protein, but not by Bid with the caspase-2 cleavage site mutated. (elsevier.com)
  • Cleavage of caspase-12 at Asp94, mediated by endoplasmic reticulum stress (ERS), contributes to stretch-induced apoptosis of myoblasts. (addgene.org)
  • Exposure of CLL cells to 0.18 micromol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. (duke.edu)
  • Through the induction of apoptosis, Apoptosis Activator 2 notably induces caspase-3 activation, PARP cleavage and DNA fragmentation. (apexbt.com)
  • Activation of apical caspases, such as caspase-8, through cell death receptors or other apoptotic stimuli leads to activation of downstream caspases, precipitous cleavage of target proteins and execution of the apoptotic program ( 7 , 8 ). (pnas.org)
  • Furthermore, both a broad-spectrum caspase inhibitor and a caspase-2-specific inhibitor blocked NIP3-induced DNA fragmentation 'in vivo', and cleavage of a caspase-2-specific substrate 'in vitro', indicating a role for caspase-2 in BNIP3-induced cell death. (umanitoba.ca)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • It is produced as a zymogen, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain. (wikipedia.org)
  • It has been shown to associate with several proteins involved in apoptosis using its CARD domain, including RIP-associated Ich-1/Ced-3-homologue protein with a death domain (RAIDD), apoptosis repressor with caspase recruitment domain (ARC), and death effector filament-forming Ced-4-like apoptosis protein (DEFCAP). (wikipedia.org)
  • Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD), caspase 2 has been shown to form the so-called PIDDosome, which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD. (wikipedia.org)
  • The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis [see comments] [published erratum appears in Nature 1999 Jul 1;400(6739):89]. (jax.org)
  • 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)
  • Zusätzlich bieten wir Ihnen Caspase 2 Kits (30) und Caspase 2 Proteine (24) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Basu, Adkins, Basu: Down-regulation of caspase-2 by rottlerin via protein kinase C-delta-independent pathway. (antikoerper-online.de)
  • In non-neuronal cells the PIDDosome, composed of caspase 2 and two death adaptor proteins, PIDD (p53-inducible protein with a death domain) and RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, has been proposed as the caspase 2 activation complex, although the absolute requirement for the PIDDosome is not clear. (sigmaaldrich.com)
  • We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. (hindawi.com)
  • Caspase-6 cleaves nuclear mitotic apparatus protein (NuMA) and mediates the shrinkage and fragmentation of nuclei. (fishersci.com)
  • Taken together, caspase 2 and caspase 3 protein levels obtained at diagnosis may constitute a reliable prognostic factor in AML. (bloodjournal.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)
  • Overexpression of the anti-apoptotic protein Bcl-2 attenuates neurodegeneration and delays activation of the caspases and fragmentation of β-actin. (jneurosci.org)
  • Bcl-2 is an integral intracellular membrane protein that inhibits programmed cell death induced by multiple insults in a wide variety of cell types ( 1 ). (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)
  • In the present study, we investigated a novel AG490 analogue, ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066), whose solubility and protein kinase-inhibitory profile suggested that this compound might be a good candidate for clinical development. (aacrjournals.org)
  • Only the viral Bcl-2 protein encoded by γHV68 was susceptible to caspase digestion. (asm.org)
  • Bcl-2 protein is normally expressed in a wide range of tissues and is required for normal development and maintenance of the immune system ( 61 ). (asm.org)
  • Interestingly, all sequenced herpesviruses of the gamma subfamily, including Epstein-Barr virus (EBV), herpesvirus saimiri (HVS), mouse gammaherpesvirus 68 (γHV68), bovine herpesvirus 4 (BHV4) Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8, equine herpesvirus 2, and ateline herpesvirus 3 encode a Bcl-2-like protein, implying a conserved requirement for viral Bcl-2 proteins. (asm.org)
  • Aβ increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. (rupress.org)
  • and (2) degradation, i.e., recognition of the Lys48 polyubiquitin chain by 26S proteasome and degradation of the target protein with generation of free ubiquitin by ubiquitin-recycling enzymes. (rupress.org)
  • For instance, FLIP blocks activation of initiator caspases, Bcl-2 prevents mitochondrial disruption, and X-linked inhibitor of apoptosis protein (XIAP) 3 inhibits downstream caspases (i.e., caspase-9 and caspase-3). (jimmunol.org)
  • This metabolic suppression of caspase-2 is exerted via the inhibitory phosphorylation of S135 on the caspase-2 prodomain by activated Ca2+/Calmodulin-dependent protein kinase II (CaMKII). (duke.edu)
  • Additionally, TT‑1 stimulated caspase‑3, caspase‑9 and Bax, and inhibited B‑cell lymphoma 2 mRNA and protein expression. (spandidos-publications.com)
  • A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al. (pubmedcentralcanada.ca)
  • Finally, we have developed a triple-transgenic mouse model (3xTg-AD) that overexpress the antiapoptotic protein, Bcl-2, in all postmitotic neurons of the CNS. (pubmedcentralcanada.ca)
  • The generation and characterization of 3xTgAD mice that overexpress the anti-apoptotic protein, Bcl-2, have been described previously [ 8 ]. (pubmedcentralcanada.ca)
  • We conclude that hypoxia results in increased expression of caspase-2 protein in the cytosolic fraction of the cerebral cortex of the newborn piglets. (ovid.com)
  • Chen YC, Shen SC, Lee WR, Lin HY, Ko CH, Shih CM, Yang LL (2002) Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1. (springer.com)
  • The study also reveals that 13-cis-retinoic acid treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-nB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells. (begellhouse.com)
  • Radiation also dramatically decreased the protein and mRNA expression of bcl-2 and increased that of bax, cytochrome c, and capase-3. (biomedcentral.com)
  • Caspase-2 requires dimerization for its activation which is primarily accomplished by recruitment to high molecular weight protein complexes in cells. (cam.ac.uk)
  • API5 protein directly binds to the caspase recruitment domain (CARD) of caspase-2 and impedes dimerization and activation of caspase-2. (cam.ac.uk)
  • The authors investigated whether gene transfer of the human antiapoptotic protein Bcl-2 by means of intratracheal adenoviral administration would preserve posttransplant lung function and reduce intragraft activated caspase activity and IL-1β production in syngeneic rat donor lung grafts. (elsevier.com)
  • grafts were then excised and protein extracts were analyzed by enzyme-linked immunosorbent assay (ELISA) and activated caspase-3 and caspase-9 assays. (elsevier.com)
  • Adenoviral overexpression of human Bcl-2 protein limits I/R injury in rat lung isografts. (elsevier.com)
  • The activation of caspase 2 occurs following the recruitment to a complex containing a p53-induced death domain protein (PIDD). (elisakits.co.uk)
  • 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)
  • Caspase-2 knockdown at the protein level was measured at 48 hours post transfection via Western Blot. (enquirebio.com)
  • Caspase 12 degrades IkappaBalpha protein and enhances MMP-9 expression in human nasopharyngeal carcinoma cell invasion. (addgene.org)
  • Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. (duke.edu)
  • Caspase-2 Polyclonal Antibody detects endogenous levels of Caspase-2 protein. (celltechgen.com)
  • This protein is highly similar to FLASH, a mouse apoptotic protein identified by its interaction with the death-effector domain (DED) of caspase 8. (genecards.org)
  • Studies of FLASH protein suggested that this protein may be a component of the death-inducing signaling complex that includes Fas receptor, Fas-binding adapter FADD, and caspase 8, and plays a regulatory role in Fas-mediated apoptosis. (genecards.org)
  • CASP8AP2 (Caspase 8 Associated Protein 2) is a Protein Coding gene. (genecards.org)
  • In mammals, a family of cysteine proteases (designated caspases) related to the Caenorhabditis elegans CED-3 protein appears to represent a major effector arm of the apoptotic program ( 5 ). (pnas.org)
  • Likewise, Apaf-1, a human protein that resembles C. elegans CED-4, interacts with caspase-9, a step that is required for the activation of the downstream protease caspase-3 ( 11 ). (pnas.org)
  • The prodomains of several apical caspases contain a protein module termed caspase recruitment domain (CARD) that is conserved in several apoptosis regulatory molecules, including Apaf-1, RAIDD, and cellular inhibitors of apoptosis proteins (IAPs) ( 12 ). (pnas.org)
  • BNIP3 is a cell death-inducing mitochondrial protein that is part of a Bcl-2 subfamily with NIX and ceBNIP3. (umanitoba.ca)
  • Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (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)
  • It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic acid residue. (wikipedia.org)
  • Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. (abcam.com)
  • Most signals that lead to apoptosis do so by activating interleukin-1β converting enzyme (ICE)-like proteases termed caspases. (bloodjournal.org)
  • Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). (sciencemag.org)
  • Caspases are a family of cytosolic aspartate-specific cysteine proteases involved in the initiation and execution of apoptosis. (neuromics.com)
  • They are expressed as latent zymogens and are activated by an autoproteolytic mechanism or by processing by other proteases (frequently other caspases). (neuromics.com)
  • For both pathways, caspases, a family of cysteine proteases, are crucial for both the initiation and execution of apoptosis. (jimmunol.org)
  • The process of apoptosis is executed by a family of cysteine proteases called caspases. (duke.edu)
  • Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type proteinase inhibitor that acts against a wide range of serine proteases through their nonproductive interaction with a P 1 residue in its first Kunitz-type domain ( 4 ). (aacrjournals.org)
  • Caspase-2 (also know as Ich-1, Nedd-2) is a member of the caspase-family of cysteine proteases. (antibody-antibodies.com)
  • 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)
  • The mammalian cell death proteases have been divided into proximal and distal caspases based on the their sites of action in the proteolytic caspase cascade ( 6 ). (pnas.org)
  • Mammalian IAP-1, -2, and XIAP directly bind and inhibit enzymatically active death proteases, caspase-3, and -7, but not the upstream protease caspase-8 ( 18 , 19 ). (pnas.org)
  • Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. (cshl.edu)
  • Caspase 2 proteolytically cleaves other proteins. (wikipedia.org)
  • Several factors are contributed in apoptosis, but the key elements are categorized in two main families of proteins including caspase enzymes and Bcl-2 family [ 18 ]. (hindawi.com)
  • Bcl-2 family is a set of cytoplasmic proteins that regulate apoptosis. (hindawi.com)
  • The two main groups of this family, Bcl-2 and Bax proteins, are functionally opposed: Bcl-2 and Bcl-x L act to inhibit apoptosis, whereas Bax counteracts this effect [ 19 , 20 ]. (hindawi.com)
  • Additionally, Bcl‑2, Bax and caspase‑3 proteins may exert a significant effect on neuron injury. (spandidos-publications.com)
  • 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)
  • More than 15 cellular Bcl-2-related proteins have been identified in a wide range of species. (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)
  • The cell damage/death was induced by non-cytotoxic type 2 ribosome-inactivating proteins: Sambucus Sieboldiana lectin (SSA) and Sambucus Nigra lectin (SNA). (alliedacademies.org)
  • They are classified as non-cytotoxic type 2 ribosome-inactivating proteins that do not have biological activities such as mitogenicity or cytotoxicity [ 11 ]. (alliedacademies.org)
  • Caspase_2, human recombinant recombinant proteins Most stable storage is at - 81 C or lower but some lyophilised proteins can be stored at +4C. (antibody-antibodies.com)
  • GENTAUR suppliers human normal cells, cell lines, RNA extracts and lots of antibodies and ELISA kits to Human proteins as well as Caspase_2, human recombinant. (antibody-antibodies.com)
  • Western blotting and reverse transcriptase PCR were used to determine the expression levels of apoptosis-related proteins and genes, including bcl-2 , bax , cytochrome c , and capase-3 . (biomedcentral.com)
  • In this dissertation, I discovered that the vaccinia virus (VACV)-encoded Bcl-2 homologue, F1L, directly inhibits caspase-9, the apical caspase in the mitochondrial cell death pathway, and NLRP1 (also known as NALP1), one of the inflammasome proteins that facilitates caspase-1 activation and cytokine secretion. (escholarship.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)
  • 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)
  • CASP2(Caspase-2) is also named as ICH1, NEDD2 and belongs to the peptidase C14A family.It is involved in the activation cascade of caspases responsible for apoptosis execution and might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.It has 2 isoforms produced by alternative splicing and can exists almost as a dimer in solution(PMID:15865942). (ptgcn.com)
  • Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (nature.com)
  • In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (nature.com)
  • This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins. (nature.com)
  • This finding highlights both an additional connection between apoptotic and autophagic pathways and a novel role for BCL-2 family proteins at the ER. (nature.com)
  • The CARD has been proposed to play a regulatory role in apoptosis by allowing proteins such as Apaf-1 to associate with caspase-9 ( 13 ). (pnas.org)
  • Two viral proteins, baculovirus p35 and cowpox virus CrmA, inhibit apoptosis by directly targeting caspases ( 14 , 15 ). (pnas.org)
  • Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. (nih.gov)
  • Taken together, our results suggest that TAIII induces HL-60 cell apoptosis through JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML. (springer.com)
  • We found that WP1066 inhibits JAK2 and its downstream STAT and PI3K pathways and induces caspase-dependent apoptosis of AML cells. (aacrjournals.org)
  • The model integrates current information concerning the signaling network downstream of Fas activation, through both type I and type II pathways, until activation of caspase-3. (jimmunol.org)
  • The pathways diverge after activation of initiator caspases (e.g., caspase-8 and caspase-10) and converge at the end by activating executor caspases (e.g., caspase-3). (jimmunol.org)
  • Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. (aacrjournals.org)
  • However, little is known about the role of TFPI-2 in the induction of apoptotic pathways in glioblastomas. (aacrjournals.org)
  • Excessive oxidative stress alters the expression levels of apoptosis-related genes and triggers sperm apoptosis through bcl-2, bax, cytochrome c and caspase-3 signaling pathways. (biomedcentral.com)
  • A significant cause of primary graft failure in lung transplantation is ischemia-reperfusion (I/R). I/R injury generates proinflammatory cytokines, such as interleukin (IL)-1β, and activates the caspase-mediated pathways of alveolar epithelial apoptosis. (elsevier.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Therefore, these compounds could be effectively used in the pharmacological manipulation of tumors characterized by resistance to cell death via either the mitochondrial or caspase-8/death receptor pathways. (unimi.it)
  • Among its related pathways are Apoptosis and survival Caspase cascade and TNFR1 Pathway . (genecards.org)
  • Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. (nature.com)
  • Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation. (cshl.edu)
  • We determined the crystal structures of apo caspase-2, caspase-2 in complex with peptide inhibitors VDVAD-CHO, ADVAD-CHO, and DVAD-CHO, and a T380A mutant of caspase-2 in complex with VDVAD-CHO. (rcsb.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)
  • Both Asp-Glu-Val-Asp-aldehyde (DEVD-cho) and Tyr-Val-Ala-Asp-chloromethylketone (YVAD-cmk), selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. (biomedsearch.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)
  • Positive regulators include cyclins, cyclin-dependent kinases (cdk), growth-stimulatory cytokines, and bcl-2, while negative regulators include p53 and the retinoblastoma (RB) genes, inhibitory cytokines, and cdk inhibitors (see Karp 1 ). (bloodjournal.org)
  • Cell-permeable and irreversible peptide inhibitors are also available for different caspases. (neuromics.com)
  • The identification of MAPK pathway genomic aberrations (NRAS mutations, loss of NF1) in primary and relapsed disease lends relevance to the use of MEK1/2 inhibitors in the treatment of neuroblastoma. (aacrjournals.org)
  • Active caspase-2 is useful in studying enzyme regulation, determining target substrates, screening caspase inhibitors, or as a positive control in caspase activity assays. (antibody-antibodies.com)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • The structures also provide a series of snapshots of caspase-2 in different catalytic states, shedding light on the mechanism of capase-2 activation, substrate binding, and catalysis. (rcsb.org)
  • These findings broaden our understanding of caspase-2 substrate specificity and catalysis. (rcsb.org)
  • In vitro assay of caspase activity carried out using poly(ADP-ribose) polymerase (PARP) as a substrate as well as intracellular caspase assays using a fluorigenic caspase-3 substrate confirmed that caspase-3 is activated in Rat-1 cells undergoing cadmium-induced apoptosis. (biomedsearch.com)
  • Here, we investigated the possibility that Bcl-2 could also serve as a caspase substrate. (sciencemag.org)
  • A fluorogenic substrate for the detection of caspase-2 (ICH-1). (merckmillipore.com)
  • Substrate of caspase-2. (agscientific.com)
  • One unit of the recombinant caspase-2 is the enzyme activity that cleaves 1 nmol of the caspase substrate VDVAD-pNA (pNA: pnitroanaline) per hour at 37°C in a reaction solution containing 50 mM Hepes, pH 7.2, 50 mM NaCl, 0.1% Chaps, 10 mM EDTA, 5% Glycerol, and 10 mM DTT. (antibody-antibodies.com)
  • A highly fluorescent substrate for caspase 1. (mobitec.com)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.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)
  • 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)
  • These effects resulted in the activation of the caspase pathway. (aacrjournals.org)
  • Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway. (sigmaaldrich.com)
  • Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. (sigmaaldrich.com)
  • Overexpression was used to distinguish among alternative hypotheses for inhibitory binding interactions of Bcl-2 with various components in the mitochondrial pathway. (jimmunol.org)
  • In the type I pathway, initiator caspases cleave and activate executor caspases directly. (jimmunol.org)
  • Caspase-2, an apoptotic initiator, can be suppressed by high levels of nutrient flux through the pentose phosphate pathway (PPP). (duke.edu)
  • Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells. (aacrjournals.org)
  • In this study, we determined whether TFPI-2 restoration could induce apoptosis through the caspase-mediated signaling pathway. (aacrjournals.org)
  • Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. (springer.com)
  • Our results indicate that the ROS→PERK→eIF2α→caspase-2 signaling pathway is central for the perception of HHP-driven cell death as immunogenic. (inserm.fr)
  • These findings imply that cell death of neurosphere cells caused by SSA or SNA is caspase-independent apoptosis via an exogenous pathway. (alliedacademies.org)
  • Recently, a new model of intrinsic pathway of apoptosis has been proposed, which suggests caspase-2 to be an initiator caspase. (semanticscholar.org)
  • Defining the DNA mismatch repair-dependent apoptotic pathway in primary cells: evidence for p53-independence and involvement of centrosomal caspase 2. (semanticscholar.org)
  • Nedd2 (caspase-2) is a cysteine protease of the caspase family that has been demonstrated to play a role in the apoptotic pathway. (mysciencework.com)
  • Silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, which in turn induced caspase 2-mediated apoptosis. (oup.com)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • Collectively, these results indicate that proteolytic activation of Bid and the subsequent induction of the mitochondrial apoptotic pathway through Bax/Bak is essential for apoptosis triggered by caspase-2. (elsevier.com)
  • To definitively rule out a role for the caspase-9/cytochrome c-dependent mitochondrial pathway of cell death, neither adenosine analog had any effect on mitochondrial membrane potential, which was instead markedly reduced by other apoptotic stimuli (e.g., deoxyribose, NaCN, and betulinic acid). (unimi.it)
  • Caspase-2, the most evolutionarily conserved member in the human caspase family, may play important roles in stress-induced apoptosis, cell cycle regulation, and tumor suppression. (rcsb.org)
  • Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. (semanticscholar.org)
  • Caspase-2 is an initiating caspase required for stress-induced apoptosis in various human cancer cells. (elsevier.com)
  • Caspase-2 Inhibitor Z-VDVAD-FMK is a synthetic peptide that irreversibly inhibits caspase-2 and related caspase activity. (agscientific.com)
  • KR disrupted the mitochondrial membrane potential and induced the release of cytochrome c and activation of caspase-3. (nih.gov)
  • In comparing model simulations with experimental results, we find the best agreement when Bcl-2 blocks the release of cytochrome c by binding to both Bax and truncated Bid instead of Bax, truncated Bid, or Bid alone. (jimmunol.org)
  • In addition, AdvBcl-2 pretreatment led to diminished cytochrome c release into cytosolic extracts and reduced intragraft IL-1β production and inhibited intragraft caspase-3 and caspase-9 activity. (elsevier.com)
  • Cytochrome C-dependent caspase activator. (hellobio.com)
  • In this study, we used both in vitro mitochondrial cytochrome c release assays and cell culture apoptosis analyses to investigate the mechanism by which caspase-2 induces apoptosis. (elsevier.com)
  • We show that active caspase-2, but neither a catalytically mutated caspase-2 nor active caspase-2 with its inhibitor, can cause cytochrome c release. (elsevier.com)
  • Caspase-2 was not able to induce cytochrome c release from Bax -/- Bak -/- mitochondria either. (elsevier.com)
  • 7BIO-induced cell death was not accompanied by cytochrome c release neither by any measurable effector caspase activation. (apexbt.com)
  • Apoptosis Activator 2 is a cell permeable compound that promotes apoptosis by activating caspases in a cytochrome c- and Apaf-1-dependent manner. (apexbt.com)
  • 20μM Apoptosis Activator 2 increases the fraction of Apaf-1 in the apoptosome when there is 0.15μM cytochrome c. (apexbt.com)
  • On the other hand, activation of caspase-8, -9, and -3, phosphorylation of Bcl-2 and Bid, and increased release of cytochrome c from mitochondria into cytosolic fraction were detected in OODBL-treated HL-60 cells. (researchwithnj.com)
  • Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene. (wikipedia.org)
  • Auf www.antikoerper-online.de finden Sie aktuell 236 Caspase 2, Apoptosis-Related Cysteine Peptidase (CASP2) Antikörper von 34 unterschiedlichen Herstellern. (antikoerper-online.de)
  • Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2) and has been shown to be required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and Aβ (β-amyloid). (sigmaaldrich.com)
  • Caspase 2 (CASP2) is an enzyme which is a class I caspases, known to contain a long pro-domain in order for nuclear localisation and is produced as a zymogen. (elisakits.co.uk)
  • Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue homogenates, cell lysates and other biological fluids. (elisakits.co.uk)
  • Caspase 2 (CASP2)- Cloud-Clone Corp. (cloud-clone.com)
  • We have identified and characterized ARC, apoptosis repressor with caspase recruitment domain (CARD). (pnas.org)
  • Caspase 2 has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. (wikipedia.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)
  • Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. (sigmaaldrich.com)
  • Caspase-9 and caspase-3 activity assays showed increased activity, indicating enhanced apoptosis. (aacrjournals.org)
  • Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Aβ neurotoxicity. (rupress.org)
  • Caspase-2 mediates death in a proportion of RGC but not photoreceptors at the site of blunt ocular trauma. (arvojournals.org)
  • Thus, caspase-2 mediates a key function in the interaction between dying cancer cells and antigen presenting cells. (inserm.fr)
  • The caspase-2 prodomain also regulates caspase-2 activity via a caspase recruitment domain that mediates oligomerization of procaspase-2 molecules and their subsequent autoactivation. (monash.edu)
  • Dimerization and autoprocessing of the Nedd2 (caspase-2) precu. (mysciencework.com)
  • Dimerization and autoprocessing of the Nedd2 (caspase-2) precursor requires both the prodomain and the carboxyl-terminal regions. (mysciencework.com)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (abcam.com)
  • Because synaptic loss, neuritic changes, and cell loss are all features of Alzheimer's disease, activation of the apoptotic cascade, especially the activation of caspases, could explain many of the features of the disease and its progression. (jneurosci.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)
  • Caspase enzymes are working as a cascade and caspase 3 is the most important member of this family which plays an effective role in apoptosis of neurons of central nervous system [ 19 ]. (hindawi.com)
  • Thus, cleaved caspase 3 could stimulate the apoptotic cascade further, and lack of its activation likely caused an accumulation of the uncleaved caspase. (bloodjournal.org)
  • Fluoride-induced headkidney macrophage cell apoptosis involves activation of the CaMKIIg-ERK 1/2-caspase-8 axis: the role of superoxide in initiating the apoptotic cascade. (fluoridealert.org)
  • We conclude that fluoride -induced apoptosis is largely dependent on Ca 2+ induced superoxide generation leading to elevation in CaMKII g which in turn induces the phosphorylation of ERK 1/2 and downstream activation of extrinsic caspase cascade in HKM cells. (fluoridealert.org)
  • We conclude that adenosine analogs induce the apoptosis of human astrocytoma cells by activating an atypical apoptotic cascade involving caspase-2 as an initiator caspase, and effector caspase-3. (unimi.it)
  • Enough time spent at pH 6 was considerably higher in the omeprazole group than in the cimetidine group Rabbit polyclonal to Caspase 2 (100% vs. 50% per treatment day time), as well as the prevalence of GI blood loss did not vary between your two groups. (mglur.info)
  • In all of the neuronal populations studied here (hippocampal neurons, sympathetic neurons, and PC12 cells), cell death was blocked by the broad spectrum caspase inhibitor N -benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone and more specifically by the downregulation of caspase-2 with antisense oligonucleotides. (jneurosci.org)
  • l , m Ectopic mahe leads to increase in number of caspase positive cells in comparison to wild type ( k ). n , o Reduction in caspase positive cells were observed upon coexpression of P35 and DIAP1 along with mahe . (nature.com)
  • Caspases play a major role in the transduction of the apoptotic signal and execution of apoptosis in mammalian cells. (fishersci.com)
  • Caspase 3 (CPP32) and Caspase 6 (Mch2) are the major active caspases in apoptotic cells, and are activated in response to distinct apoptosis-inducing stimuli in all cell lines analyzed. (fishersci.com)
  • Using quantitative Western blot analysis, we studied the levels of nonactivated (uncleaved) caspase 2 and 3 in peripheral blood low-density cells from 185 patients with newly diagnosed AML. (bloodjournal.org)
  • 11 In addition, activation of caspase 3 and, to some extent, caspase 2 (ICH-1) 12-16 appears to be necessary to induce apoptosis in HL-60 myeloid leukemia cells. (bloodjournal.org)
  • These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity. (biomedsearch.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)
  • Bcl-2 is cleaved by caspases both in vitro and in intact cells. (sciencemag.org)
  • B ) COS-1 cells (5 × 10 5 ) were cotransfected using lipofectamine (Life Technologies) with equal amounts of DNA [2 μg of each of the indicated expression plasmids + control vector pSG5 control vector (Stratagene) as required] and cell lysates were immunoblotted 24 hours after transfection with antibody to Bcl-2 (from D. Mason). (sciencemag.org)
  • C ) Jurkat cells were treated with anti-Fas (1 μg/ml) for 2 hours with or without a 30-min pretreatment with 300 mM Ac-DEVD-CHO, then assessed for viability by trypan blue exclusion in three independent experiments, and the percentage of viable cells was calculated relative to untreated cells. (sciencemag.org)
  • D ) Jurkat cells treated as in (C) were immunoblotted with Bcl-2 antibody 100 (Santa Cruz). (sciencemag.org)
  • Caspase 10/b Immunoblotting of SDS-extracts from 2 x 105 human Jurkat cells. (neuromics.com)
  • Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). (aacrjournals.org)
  • Because ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. (aacrjournals.org)
  • KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. (asm.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)
  • Our inhibitor studies further implicated CaMKII g in the activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) culminating in caspase-8/caspase-3 mediated apoptosis of HKM cells. (fluoridealert.org)
  • Human coronary artery endothelial cells (HCAEC) were treated with a combination of tumour necrosis factor-alpha and interleukin-1 alpha then incubated with NE for 2 or 6 h. (bmj.com)
  • Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. (aspetjournals.org)
  • In in vivo experiments, xenografts of bcl-2 -transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells. (aspetjournals.org)
  • Using a recombinant adeno-associated viral vector carrying human TFPI-2 cDNA, we stably expressed TFPI-2 in U-251 cells, a highly invasive human glioblastoma cell line. (aacrjournals.org)
  • The results from nuclear chromatin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and fluorescence-activated cell sorting analysis showed increased apoptosis in U-251 cells after restoration of TFPI-2. (aacrjournals.org)
  • A wide variety of cells, including keratinocytes ( 5 ), dermal fibroblasts ( 5 ), smooth muscle cells ( 6 ), synoviocytes ( 7 ), and endothelial cells ( 8 ), synthesize and secrete TFPI-2 primarily into the extracellular matrix (ECM). (aacrjournals.org)
  • Three isoforms of TFPI-2 are synthesized by these cells and migrate with an apparent molecular weight of 33, 31, and 27 kDa due to differential glycosylation ( 9 ). (aacrjournals.org)
  • Results: The TF signaling complexes were shown to prevent apoptosis induced by serum starvation and TRAIL in cancer cells by reduced activation of caspase-8 in a PI3k/AKT-dependent manner. (diva-portal.org)
  • In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4′-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. (springer.com)
  • 13-cis-retinoic acid treatment also showed an inhibitory effect on bcl-2 expression and upregulated p53 and caspase-3 gene expression in B16F-10 melanoma cells. (begellhouse.com)
  • Non-phosphorylatable eIF2α, depletion of PERK, caspase-2 or -8 compromised calreticulin exposure by cancer cells succumbing to HHP but could not inhibit death. (inserm.fr)
  • Interestingly, the phagocytosis of HHP-treated malignant cells by dendritic cells was suppressed by the knockdown of caspase-2 in the former. (inserm.fr)
  • Although caspase-2 is imported into the nucleus, mutants lacking the NLS were still capable of inducing apoptosis upon overexpression in transfected cells. (monash.edu)
  • Additionally, the cells were not rescued from cell death even under the presence of a pan-caspase inhibitor. (alliedacademies.org)
  • They have been used in a wide range of studies, such as neural stem cell (NSC) identification and isolation, proliferation and maintenance of NSCs, and differentiation of NSCs into neuronal and glial cells [ 2 - 7 ]. (alliedacademies.org)
  • Similar to other caspases, caspase-2 also exists in cells as an inactive proenzyme. (antibody-antibodies.com)
  • In cells, F1L specifically represses caspase-9- dependent apoptosis and NLRP1-dependent IL-1[Beta] secretion. (escholarship.org)
  • Consistently, loss of API5 sensitizes cells to caspase-2-dependent apoptotic cell death. (cam.ac.uk)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours. (wikipedia.org)
  • Nano - drug Delivery of Apoptosis Activator 2 to AGS Cells by Liposomes Conjugated with Anti-TROP2 Antibody. (hellobio.com)
  • U-2 OS Human Osteosarcoma Epithelial Cells from Bone. (enquirebio.com)
  • However, it is not clear how caspase-2 exerts its apoptotic function in cells and whether its enzymatic activity is required for the apoptotic function. (elsevier.com)
  • In cultured cells, gene deletion of Bax/Bak or Bid abrogated apoptosis induced by overexpression of caspase-2. (elsevier.com)
  • Both the anticancer agent 2-chloro-2'-deoxy-adenosine (Cladribine) and its derivative 2-chloro-adenosine induce apoptosis of human astrocytoma cells (J Neurosci Res 60:388-400, 2000). (unimi.it)
  • A key role for caspase-2 and caspase-3 in the apoptosis induced by 2-chloro-2'-deoxy-adenosine (cladribine) and 2-chloro-adenosine in human astrocytoma cells / S. Ceruti, E. Beltrami, P. Matarrese, A. Mazzola, F. Cattabeni, W. Malorni, M. P. Abbracchio. (unimi.it)
  • Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. (duke.edu)
  • These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl-2 modulation, the presence of IL-4, or p53 status. (duke.edu)
  • Caspase-2 is usually triggered pursuing a range of mobile insults (metabolic discrepancy, DNA harm)11 and activates additional caspases to both initiate and amplify the apoptosis transmission.12 Latest data recommend that MEFs are more resistant to apoptosis induced by microtubule and spindle toxins16 and display increased DNA harm following irradiation,13 recommending that reduction may promote success of NVP-BEP800 cells with damaged DNA. (techtasys.com)
  • A common feature of the tumours from these mouse versions can be elevated chromosomal lack of stability and aneuploidy.13, 14, 18, 19, 21, 22 These findings suggest that caspase-2 may protect cells against KIAA1819 tumorigenic and aneuploidy potential. (techtasys.com)
  • It can be also uncertain whether aneuploidy noticed in tumours and MEFs can be a outcome of caspase-2 function in marketing apoptosis of mitotically extravagant cells or credited to various other jobs of caspase-2 in cell routine. (techtasys.com)
  • To address this crucial issue, we set up an program for aneuploidy using major cells or utilized a human being cell collection acutely exhausted of caspase-2. (techtasys.com)
  • Our data display an essential part for caspase-2 in restricting aneuploidy by removing chromosomally unpredictable cells, at least in component Bid-mediated apoptosis. (techtasys.com)
  • We also examined the importance of caspase-2 catalytic activity in removing chromosomally unpredictable cells by producing a mutant mouse. (techtasys.com)
  • Our outcomes demonstrate that in the lack of caspase-2 activity, cells with faulty mitosis become multinucleated and are capable to survive lengthy term. (techtasys.com)
  • Our function determines a crucial part for caspase-2 in the effective apoptotic removal of possibly tumorigenic cells and provides a basis for the tumor suppressor function of caspase-2. (techtasys.com)
  • Outcomes lacking cells are a book model of aneuploidy To check how caspase-2 reduction might business lead to aneuploidy, we used a cell program. (techtasys.com)
  • Apoptosis Activator 2 is a cell-permeable indoledione activator of caspases with IC50 value of 4-9 μM for leukemia cells. (apexbt.com)
  • Further analysis showed that the enzymatic activity of caspase-8 was inhibited by ARC in 293T cells. (pnas.org)
  • An ' in vitro' caspase assay detected activation of endogenous caspase-2 in BNIP3-transfected cells. (umanitoba.ca)
  • This activation corresponded with enhanced cell death and DNA fragmentation in cells co-expressing BNIP3 and caspase-2. (umanitoba.ca)
  • 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)
  • The data demonstrate that cell death is prevented during mitosis through the inhibitory phosphorylation of caspase-2 and suggest that under conditions of mitotic arrest, cdk1-cyclin B1 activity must be overcome for apoptosis to occur. (antikoerper-online.de)
  • Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. (springer.com)
  • Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2α phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation. (inserm.fr)
  • however, caspase 2 inhibitor also reversed p53 phosphorylation suggesting a bidirectional regulation between them. (oup.com)
  • 7BIO inhibited FLT3, the dual-specificity tyrosine phosphorylation-regulated kinases, DYRK1A and DYRK2 with the IC50 values of 0.34 μM, 1.9 and 1.3 μM, respectively [2]. (apexbt.com)
  • Some prior findings recommend that caspase-2 provides a function NVP-BEP800 in mitotic failure.5 Caspase-2 phosphorylation by Cdk1Ccyclin B1 complicated has been suggested as a factor as one mechanism that can prevent caspase-2 activation and cell loss of life,12 promoting mitotic slippage thereby. (techtasys.com)
  • 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)
  • Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. (semanticscholar.org)
  • Specificity This assay has high sensitivity and excellent specificity for detection of CASPASE-2. (biobool.com)
  • Caspases-1, -8, and -9, which have homologous prodomains to caspase-2, do not bind BNIP3 or NIX, indicating specificity for caspase-2. (umanitoba.ca)
  • Our study also suggests that modulation of caspase activity may provide protective benefit in the treatment of ALS, a view that is consistent with our recent demonstration of caspase inhibition extending the survival of transgenic mSOD1 mice. (jneurosci.org)
  • Conclusions: Synergistic activity of combined MEK1/2 and PI3K inhibition in human neuroblastoma cell lines via the induction of apoptosis was observed. (aacrjournals.org)
  • Combined MEK1/2 and PI3K inhibition induces synergistic caspase-dependent apoptosis in neuroblastoma. (aacrjournals.org)
  • The interpretation of this finding was the observed accumulation of APP and tau resulted from an inhibition in caspasemediated proteolysis following overexpression of Bcl-2. (pubmedcentralcanada.ca)
  • After Src kinase inhibition followed by hypoxia, caspase-2 expression was similar to normoxia levels. (ovid.com)
  • We identified two conserved motifs at the N- terminus of F1L preceding the Bcl-2-like domain by mutagenesis studies that are responsible for interaction and inhibition of caspase-9 and NLRP1, respectively. (escholarship.org)
  • 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)
  • Consistent with the inhibition of caspase-8, ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis factor-R1, and TRAMP/DR3. (pnas.org)
  • The activated caspases abrogate the effect of substrates that protect cellular integrity, such as the DNA-repair enzyme poly(ADP-ribose) polymerase (PARP), and thereby induce apoptotic cell death. (bloodjournal.org)
  • The active caspase-2 preferentially cleaves caspase-2 substrates (e.g. (antibody-antibodies.com)
  • 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)
  • Caspase-2 is unique among mammalian caspases because it localizes to the nucleus in a prodomain-dependent manner. (monash.edu)
  • In this study we sought to map specific functional regions in the caspase-2 prodomain that regulate its nuclear transport and also its activation. (monash.edu)
  • Our data indicate that caspase-2 contains a classical nuclear localization signal (NLS) at the C terminus of the prodomain which is recognized by the importin α/β heterodimer. (monash.edu)
  • We define a region in the prodomain that regulates the ability of caspase-2 to form dot- and filament-like structures when ectopically expressed, which in turn promotes cell killing. (monash.edu)
  • The interaction is unique in that it is not mediated through the caspase-2 prodomain. (umanitoba.ca)
  • Interestingly, recombinant API5 directly inhibits full length but not processed caspase-2. (cam.ac.uk)
  • By comparing the apo and inhibited caspase-2 structures, we propose that the disruption of a non-conserved salt bridge between Glu-217 and the invariant Arg-378 is important for the activation of caspase-2. (rcsb.org)
  • Consistent with this, herein we show that the spinal cord of transgenic mSOD1 mice is the site of the sequential activation of caspase-1 and caspase-3. (jneurosci.org)
  • Collectively, our data indicate that activation of caspase-3 is a prominent feature of mSOD1-induced neurodegeneration. (jneurosci.org)
  • This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. (rupress.org)
  • E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress-mediated Aβ neurotoxicity. (rupress.org)
  • Here we show that E2-25K/Hip-2 regulates the activation of caspase-12 and ER stress responses during Aβ neurotoxicity, and that E2-25K/Hip-2-deficient cortical neurons cultured from E2-25K/Hip-2 knockout mice lack Aβ-induced ER stress responses, including accumulation of caspase-12, and are resistant to Aβ toxicity. (rupress.org)
  • The abnormalities in the fetal thyroid gland seemed to depend on the activation of caspase-3, Bcl-2, BAX, Cox2, and NF-κB mRNA expression. (rsc.org)
  • drugs blocking the activation of Caspase-1 have been used to improve the health of patients. (wikipedia.org)
  • We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. (cshl.edu)
  • Taken together, our results suggest that BNIP3 induces DNA fragmentation and subsequent cell death through a novel mechanism involving the specific recruitment and activation of caspase-2. (umanitoba.ca)
  • The mature protease can process its own propeptide, but not that of other caspases. (abcam.com)
  • 15 16 Caspase 3 is a cysteine protease homologous with ICE. (bloodjournal.org)
  • Global Markets Direct's, 'Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC - Pipeline Review, H2 2016', provides in depth analysis on Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC targeted pipeline therapeutics. (reportsnreports.com)
  • The report provides comprehensive information on the Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC, targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
  • Additionally, the report provides an overview of key players involved in Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC targeted therapeutics development and features dormant and discontinued projects. (reportsnreports.com)
  • Programmed cell death (Apoptosis) and cytokine secretion, which are mediated by activation of different caspase-family protease cascades, are examples of the numerous mechanisms of our innate immunity against viral infections. (escholarship.org)
  • 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)
  • The minimum detection sensitivity level of a caspase-2 using this human caspase 2 ELISA kit was 0.121 ng/ml. (elisakits.co.uk)
  • Intended Use Human Caspase 2 ELISA Kit allows for the in vitro quantitative determination of Caspase 2 , concentrations in serum, Plasma , tissue homogenates and Cell culture supernates and Other biological fluids. (biobool.com)
  • Inquiry About Human Caspase 2 ELISA Kit If you hope to order it or contact us directly, please contact us via [email protected] (biobool.com)
  • This CASPASE-2 ELISA kit is a 1.5 hour solid-phase ELISA designed for the quantitative determination of Human CASPASE-2. (biobool.com)
  • Principle of the Assay: CASPASE-2 ELISA kit applies the competitive enzyme immunoassay technique utilizing a monoclonal anti-CASPASE-2 antibody and an CASPASE-2-HRP conjugate. (biobool.com)
  • Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction. (wikipedia.org)
  • To investigate the requirement for the PIDDosome in caspase-2-dependent neuronal death, we have examined the necessity for each component in induction of active caspase 2 and in execution of caspase-2-dependent neuronal death. (sigmaaldrich.com)
  • We find that both NGF deprivation and Aβ treatment of neurons induce active caspase 2 and that induction of this activity depends on expression of RAIDD, but is independent of PIDD expression. (sigmaaldrich.com)
  • Finally, we find that E2-25K/Hip-2-deficient cortical neurons are resistant to Aβ toxicity and to the induction of ER stress and caspase-12 expression by Aβ. (rupress.org)
  • In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. (springer.com)
  • Overall, it appears that caspase 2 is a very versatile caspase that has multiple functions beyond cell death induction. (elisakits.co.uk)
  • Moreover, the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone (fmk) suppressed both caspase-3 activation and apoptosis induction. (unimi.it)
  • According to the Aβ hypothesis, Aβ precedes NFT formation, suggesting that Aβ may be the earliest event that triggers downstream events [ 2 ]. (pubmedcentralcanada.ca)
  • Caspase-2 Monoclonal antibody specifically detects Caspase-2 in Human samples. (fishersci.com)
  • Ensure accurate, reproducible results in western blotting and immunoprecipitation procedures with Thermo Scientific Caspase 6 (Mch 2) Ab-3, Mouse Monoclonal Antibody. (fishersci.com)
  • These results were confirmed utilizing a similar site-directed antibody to caspase-cleaved APP (APPneo). (pubmedcentralcanada.ca)
  • The cytosolic brain function was isolated and a western blot analysis was carried out using an antibody specific for the caspase-2. (ovid.com)
  • The intensity of the color is inversely proportional to the CASPASE-2 concentration since CASPASE-2 from samples and CASPASE-2-HRP conjugate compete for the anti-CASPASE-2 antibody binding site. (biobool.com)
  • Our previous studies showed that restoration of TFPI-2 in glioblastomas effectively prevents cell proliferation, angiogenesis, and tumor invasion. (aacrjournals.org)
  • Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1-associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • Glioblastomas comprise 23% of primary brain tumors in the United States and are the most commonly diagnosed brain tumor in adults ( 2 ). (aacrjournals.org)
  • Recent studies have shown that TFPI-2 expression plays a significant role in inhibiting tumor invasion and metastasis by a mechanism that involves its inhibitory activity ( 11 - 13 ). (aacrjournals.org)
  • These data seem to question a general tumor-suppressive role of caspases. (mdpi.com)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. (mdpi.com)
  • Although they normally develop, prior research have got set up that rodents present improved susceptibility to tumorigenesis marketed by and rodents,21 and diethylnitrosamine-mediated hepatocellular carcinoma,22 suggesting a function for caspase-2 as a tumor suppressor. (techtasys.com)
  • Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (wikipedia.org)
  • Pro-caspase-2 contains two subunits, p19 and p12. (wikipedia.org)
  • The cleaved form of caspase 3 consists of biologically active subunits p17 and p12. (bloodjournal.org)
  • In addition, caspases cleave the proenzyme precursors to produce the active subunits of caspases themselves ( 8 ). (sciencemag.org)
  • The processed active caspase-2 is a heterotetramer consisting of two large (19 kDa) and two small (12 kDa) subunits. (antibody-antibodies.com)
  • Pro-caspase-2 contains two subunits, p19 and p12.In addition, caspase 2 may form a complex with the catalytic subunit of DNA-PK (DNA-PKcs) and PIDD (LRDD), which is involved in DNA repair after DNA damage. (cloud-clone.com)
  • The caspases are synthesized as inactive precursors that are proteolytically processed to generate active subunits. (pnas.org)
  • d , d ′ mahe induced eye phenotype was suppressed by expression of P35 , an inhibitor of effector caspase. (nature.com)
  • There has been a considerable debate as to whether caspase-2 is an initiator or effector caspase. (semanticscholar.org)
  • Both compounds produced a gradual and time-dependent activation of 'effector' caspase-3, which preceded the appearance of the nuclear signs of apoptosis, suggesting a temporal correlation between these two events. (unimi.it)
  • Previous studies have shown that aggregated Aβ can induce caspase-dependent apoptosis in cultured neurons. (jneurosci.org)
  • Neurons from caspase-2 null mice were totally resistant to Aβ 1-42 toxicity, confirming the importance of this caspase in Aβ-induced death. (jneurosci.org)
  • We show that treatment of wild-type or PIDD-null neurons with Aβ or NGF deprivation induces formation of a complex of caspase 2 and RAIDD. (sigmaaldrich.com)
  • We also show that caspase-2-dependent execution of neurons requires RAIDD, not PIDD. (sigmaaldrich.com)
  • Caspase 2 activity can be induced in neurons from PIDD-null mice, and NGF deprivation or Aβ use caspase 2 and RAIDD to execute death of these neurons. (sigmaaldrich.com)
  • In the present study, we demonstrate (1) that caspase-1 and caspase-3 are activated sequentially in the spinal cords of affected transgenic mSOD1 mice, (2) that activated caspase-3 is localized within neurons of the anterior horn that exhibit apoptotic features, and (3) that overexpression of Bcl-2 delays caspase activation in these animals. (jneurosci.org)
  • The neurons expressing caspase‑3, Bax and Bcl‑2 in the cortical area, CA3, CA1, stratum lucidum (Slu) and molecular layer of the dentate gyrus (MoDG) of the hippocampus were detected using immunohistochemistry or the TUNEL method. (spandidos-publications.com)
  • 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)
  • Elevated P75NTR expression causes death of engrailed-deficient midbrain dopaminergic neurons by Erk1/2 suppression. (hellobio.com)
  • In vitro translated human Bcl-2 was digested with purified recombinant caspase-3 (CPP32). (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)
  • Alternatively, Jurkat cell lysates were digested for 4 hours with recombinant caspase-3. (sciencemag.org)
  • Please read carefully the data sheet of the Caspase_2, human recombinant. (antibody-antibodies.com)
  • Caspase_2, human recombinant Human samples 80 % of the research is conducted on human samples. (antibody-antibodies.com)
  • The recombinant active human caspase-2 was expressed in E. coli. (antibody-antibodies.com)
  • Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2-mediated cell death. (rupress.org)
  • To elucidate critical signaling network properties, we examined the effects of altering the level of Bcl-2 on the kinetics of caspase-3 activation, using both overexpression and knockdown in the model and experimentally. (jimmunol.org)
  • Moreover, although Bcl-2 overexpression strongly reduces caspase-3 activation, Bcl-2 knockdown has a negligible effect, demonstrating a general model finding that varying the expression levels of signal molecules frequently has asymmetric effects on the outcome. (jimmunol.org)
  • Small interfering RNA-mediated caspase-2 knockdown neuroprotected RGC around but not in the center of the injury site. (arvojournals.org)
  • In addition, caspase-2 knockdown increased the amplitude of the ERG photopic negative response (PhNR) at 2 weeks after injury. (arvojournals.org)
  • An additional finding of that study was the accumulation of full-length APP and tau following overexpression of Bcl-2 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)
  • Human Bcl-2 transgene overexpression in donor lung grafts was demonstrated by ELISA of tissue homogenates. (elsevier.com)
  • Cooke, DT , Hoyt, EG & Robbins, RC 2005, ' Overexpression of human Bcl-2 in syngeneic rat donor lungs preserves posttransplant function and reduces intragraft caspase activity and interleukin-1β production ', Transplantation , vol. 79, no. 7, pp. 762-767. (elsevier.com)
  • Caspases are key enzymes responsible for mediating apoptotic cell death. (cam.ac.uk)
  • Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. (semanticscholar.org)
  • in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. (cshl.edu)
  • Activates caspase-3 following caspase-9 activation. (hellobio.com)
  • It exists in an inactive caspase pro-enzyme from which needs to undergo a proteolytic process that can be located to the conserved aspartic residues. (elisakits.co.uk)
  • Each caspase contains conserved sequences important for proteolytic activity cleaving after specific aspartic acid residues ( 6 ). (pnas.org)
  • Levels of endoplasmic reticulum (ER)-resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. (rupress.org)
  • Abcam's Caspase 2 Assay Kit (Fluorometric) provides a simple and convenient means for assaying the activity of caspases that recognize the sequence VDVAD. (abcam.com)
  • Growing evidence has implicated aberrant caspase activity in the neurodegeneration associated with AD and Huntington's disease, as well as other unrelated pathologies. (sciencemag.org)
  • Neuronal caspase 2 activity and function requires RAIDD, but not PIDD. (sigmaaldrich.com)
  • Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. (hindawi.com)
  • All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (γHV68) and bovine herpesvirus 4 (BHV4), as described here. (asm.org)
  • However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. (asm.org)
  • Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. (rupress.org)
  • Thus, a fuller understanding of the mechanisms involved in regulating ER stress, caspase-12 activity, and their roles in Aβ neurotoxicity would be highly desirable. (rupress.org)
  • However, a critical mediator coordinating ER stress and caspase-12 activity in Aβ neurotoxicity remains unknown. (rupress.org)
  • TFPI-2 exhibits strong inhibitory activity toward a broad spectrum of proteinases, including trypsin, plasmin, chymotrypsin, cathepsin G, plasma kallikrein, and the factor VIIa-tissue factor complex. (aacrjournals.org)
  • In contrast, TFPI-2 exhibits little or no inhibitory activity toward urokinase-type plasminogen activator, tissue-type plasminogen activator, and α-thrombin ( 10 ). (aacrjournals.org)
  • The lyophilized caspase-2 is stable for 1 year at -70°C. Following reconstitution in PBS, the enzyme should be aliquoted and immediately stored at -70°C. Avoid multiple freeze/thaw cycles as activity might decrease. (antibody-antibodies.com)
  • We recommend using 1 unit/assay for analyzing caspase activity. (antibody-antibodies.com)
  • Pan-caspase inhibitor with in vivo activity (Ki values 18.4 μM, 0.45 μM, and 17.1 μM for Caspase-3, -8, and -9 resp). (axonmedchem.com)
  • The Caspase-2 Inhibitor I controls the biological activity of Caspase-2. (emdmillipore.com)
  • Conversely, 1 to 7 h after addition of either adenosine analog (i.e., before the appearance of caspase-3 activation), caspase-2 activity was surprisingly and markedly increased. (unimi.it)
  • Little is known about the regulation of caspase activity during apoptosis. (pnas.org)
  • However, BNIP3-induced cell death is independent of caspase-3 activity, thus the mechanism of BNIP3-induced DNA fragmentation remains unknown. (umanitoba.ca)
  • Cadmium induces caspase-mediated cell death: suppression by Bcl-2. (biomedsearch.com)
  • Apoptosis is a process of active cell death and is characterized by activation of caspases, DNA fragmentation, and biochemical and morphological changes. (biomedsearch.com)
  • Expression of Bcl-2 or CrmA each suppressed cadmium-induced cell death although Bcl-2 was somewhat more effective than CrmA. (biomedsearch.com)
  • However, the nonselective caspase inhibitor, z-Val-Ala-Asp-floromethylketone (zVAD-fmk), was the most efficacious agent, almost completely blocking cadmium-induced cell death. (biomedsearch.com)
  • Taken together, these results demonstrate that as in other forms of apoptosis, caspases play a central role in cadmium-induced cell death. (biomedsearch.com)
  • Fig. 2: Ectopic expression of mahe promotes caspase-dependent dosage sensitive cell death in eye tissue of Drosophila. (nature.com)
  • p ) Graph represents intensity of cl-casp3 per unit area showing mahe triggers caspase-dependent cell death, which was suppressed by P35 and DIAP1 . (nature.com)
  • Because caspase activation is an essential step in programmed cell death (apoptosis) and cytotoxic drug-induced apoptosis is mediated by caspase 2 and caspase 3, we hypothesized that caspase 2 and 3 levels predict clinical outcome in acute myelogenous leukemia (AML). (bloodjournal.org)
  • Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. (biomedsearch.com)
  • Both biochemical and genetic evidence indicates that Bcl-2 family members can regulate cell death induced by caspases ( 2 ). (sciencemag.org)
  • Furthermore, the cell death response was rescued by treatment with the caspase inhibitory peptide, QVD-OPh. (aacrjournals.org)
  • The bcl-2 gene was identified at chromosomal translocation breakpoints in follicular lymphomas and contributes to tumorigenesis by inhibiting programmed cell death rather than by stimulating cell growth ( 1 , 59 ). (asm.org)
  • Caspase-2-dependent cell death is important and evidenced in models of RGC degeneration. (arvojournals.org)
  • Cagnol S, Van Obberghen-Schilling E, Chambard JC (2006) Prolonged activation of ERK1, 2 induces FADD-independent caspase 8 activation and cell death. (springer.com)
  • Those data also revealed dispensability of caspase-3, although we found this caspase critical for ovarian granulosa cell death. (semanticscholar.org)
  • Apart from cell death, caspase-2 also regulates autophagy, genomic stability and ageing. (cam.ac.uk)
  • 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)
  • 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)
  • [5] The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. (wikipedia.org)
  • Most caspases play a role in programmed cell death. (wikipedia.org)
  • 7-bromoindirubin-3'-oxime (7BIO), a derivative of indirubin, is a caspase independent nonapoptotic cell death inducer [1]. (apexbt.com)
  • 7-Bromoindirubin-3′-oxime induces caspase-independent cell death[J]. Oncogene, 2006, 25(47): 6304-6318. (apexbt.com)
  • Accordingly, at concentrations that selectively inhibit these caspases, neither N-benzyloxycarbonyl-Leu-Glu-His-Asp-fmk nor N-benzyloxycarbonyl-Ile-Glu-Thr-Asp-fmk could prevent adenosine analog-induced cell death. (unimi.it)
  • The selective caspase-2 inhibitor N-benzyloxy carbonyl-Val-Asp-Val-Ala-Asp-fmk significantly reduced both adenosine analogs-induced caspase-2 activation and the associated cell death. (unimi.it)
  • The CARD domain of ARC exhibited significant homology to the prodomains of apical caspases and the CARDs present in the cell death regulators Apaf-1 and RAIDD. (pnas.org)
  • Apoptosis, a morphologically distinguished form of programmed cell death, is critical not only during development and tissue homeostasis but also in the pathogenesis of a variety of diseases including cancer, autoimmune disease, viral infection, and degenerative disorders ( 1 , 2 ). (pnas.org)
  • DNA fragmentation during most types of apoptosis is predominantly due to caspase-3 activation. (umanitoba.ca)
  • It is also known as caspase activated nuclease (CPAN), dna fragmentation factor 40 (DFF-40), DFF2 and DFFB. (wikipedia.org)
  • Conversely, a high level of cleaved caspase 3 denoted improved survival and correlated with the inactivation of the DNA-repair enzyme poly(ADP-ribose) polymerase. (bloodjournal.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)
  • Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
  • The sequential activation of caspases is important in the execution-phase of cell apoptosis. (elisakits.co.uk)
  • The work reported here examines which of the caspases is required for Aβ to induce apoptosis. (jneurosci.org)
  • Our data provides a mechanism for caspase-2 nuclear import and demonstrate that association of procaspase-2 into higher order structures, rather than its nuclear localization, is required for caspase-2 activation and its ability to induce apoptosis. (monash.edu)
  • Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. (duke.edu)