Caspases effector. Medical search

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.

Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

A 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 short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.

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.

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 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.

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.

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.

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.

A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.

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.

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.

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.

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.

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.

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 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.

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.

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)

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)

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.

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 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.

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.

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.

The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.

Established cell cultures that have the potential to propagate 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.

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.

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.

A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.

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.

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.

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 cell line derived from cultured tumor cells.

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 altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.

Peptides composed of between two and twelve amino acids.

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.

A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.

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.

Transport proteins that carry specific substances in the blood or across cell membranes.

Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

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.

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.

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 critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

A 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.

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.

The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.

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.

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.

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.

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.

Physiologically inactive substances that can be converted to active enzymes.

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.

Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

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.

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)

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.

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.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.

Proteins found in any species of bacterium.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.

A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.

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.

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 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.

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.

A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.

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)

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Glycoproteins found on the membrane or surface of cells.

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.

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.

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.

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.

CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.

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

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.

Elements of limited time intervals, contributing to particular results or situations.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

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.

Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.

In GRAM NEGATIVE BACTERIA, multiprotein complexes that function to translocate pathogen protein effector molecules across the bacterial cell envelope, often directly into the host. These effectors are involved in producing surface structures for adhesion, bacterial motility, manipulation of host functions, modulation of host defense responses, and other functions involved in facilitating survival of the pathogen. Several of the systems have homologous components functioning similarly in GRAM POSITIVE BACTERIA.

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.

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.

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.

Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

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.

The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

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.

A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

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.

A species of gram-negative, fluorescent, phytopathogenic bacteria in the genus PSEUDOMONAS. It is differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities.

Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.

Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.

Diseases of plants.

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.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.

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.

The rate dynamics in chemical or physical systems.

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.

Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).

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.

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.

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.)

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.

Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.

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.

The interactions between a host and a pathogen, usually resulting in disease.

The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.

Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)

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.

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.

Dried aged bark of a buckthorn, Frangula purshiana (FRANGULA), that contains the anthraquinone EMODIN and cascarosides. It is used as a laxative (CATHARTICS).

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

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.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.

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)

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.

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.

Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.

A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

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.

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.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

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.

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.

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.

Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

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).

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 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).

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 short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.

An encapsulated lymphatic organ through which venous blood filters.

Antibodies produced by a single clone of cells.

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.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

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.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

The process of cleaving a chemical compound by the addition of a molecule of water.

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.

Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.

Proteins found in any species of virus.

Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.

A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.

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.

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.

A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.

Eukaryotes in the group STRAMENOPILES, formerly considered FUNGI, whose exact taxonomic level is unsettled. Many consider Oomycetes (Oomycota) a phylum in the kingdom Stramenopila, or alternatively, as Pseudofungi in the phylum Heterokonta of the kingdom Chromista. They are morphologically similar to fungi but have no close phylogenetic relationship to them. Oomycetes are found in both fresh and salt water as well as in terrestrial environments. (Alexopoulos et al., Introductory Mycology, 4th ed, pp683-4). They produce flagellated, actively motile spores (zoospores) that are pathogenic to many crop plants and FISHES.

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.

Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.

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.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

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.

Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.

Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.

The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.

Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.

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.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

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.

A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.

Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.

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.

Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.

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.

The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

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.

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 degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.

A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: regulation by the ERK1/2 MAP kinase pathway. (1/11)

This study was designed to assess the effects of opiate treatment on the expression of Fas-associated protein with death domain (FADD) in the rat brain. FADD is involved in the transmission of Fas-death signals that have been suggested to contribute to the development of opiate tolerance and addiction. Acute treatments with high doses of sufentanil and morphine (mu-agonists), SNC-80 (delta-agonist), and U50488H (kappa-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine). The cannabinoid CB1 receptor agonist WIN 55,212-2 did not alter FADD content in the brain. Chronic (5 days) morphine (10-100 mg/kg), SNC-80 (10 mg/kg), or U50488H (10 mg/kg) was associated with the induction of tachyphylaxis to the acute effects. In morphine- and SNC-80-tolerant rats, antagonist-precipitated (2 h) or spontaneous withdrawal (24-48 h) induced a new and sustained inhibition of FADD (13-50%). None of these treatments altered the densities of caspases 8/3 (including the active cleaved forms) in the brain. Pretreatment of rats with SL 327 (a selective MEK1/2 inhibitor that blocks ERK activation) fully prevented the reduction of FADD content induced by SNC-80 in the cerebral cortex (43%) and corpus striatum (29%), demonstrating the direct involvement of ERK1/2 signaling in the regulation of FADD by the opiate agonist. The results indicate that mu- and delta-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment. Opiate drugs (and specifically the delta-agonists) could promote survival signals in the brain through inhibition of FADD, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway. (+info)

Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus. (2/11)

Members of the baculovirus p35 gene family encode proteins that specifically inhibit caspases, cysteine proteases that are involved in apoptosis. To date, p35 homologs have only been found in baculoviruses. We have identified AMVp33, a gene from Amsacta moorei entomopoxvirus with low but significant homology to baculovirus p35 genes. Expression of AMVp33 blocked apoptosis in several different insect and human cell lines. Purified recombinant P33 protein was an efficient inhibitor of insect and human effector caspases, but not initiator caspases. P33 was cleaved by effector caspases, and the resulting cleavage fragments stably associated with the caspases. Mutation of the predicted caspase cleavage site in P33 eliminated cleavage, caspase inhibition and anti-apoptotic function. Thus, AMVp33 encodes a caspase inhibitor similar to baculovirus P35 with a preference for effector caspases. This is the first report of a p35 homolog from any viral or cellular genome outside of the baculovirus family. (+info)

Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop. (3/11)

(+info)

Reactive-site cleavage residues confer target specificity to baculovirus P49, a dimeric member of the P35 family of caspase inhibitors. (4/11)

(+info)

Inactivation of effector caspases through nondegradative polyubiquitylation. (5/11)

(+info)

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring. (6/11)

(+info)

Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. (7/11)

(+info)

Gene expression in the brain during reovirus encephalitis. (8/11)

(+info)

Broz P, Monack DM (February 2013). "Noncanonical inflammasomes: caspase-11 activation and effector mechanisms". PLOS Pathogens ... Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by ... Caspase-11 activation by direct binding to LPS represents a novel and unprecedented mechanism for caspase activation. Caspase- ... "Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions". The Journal of Cell ...

https://en.wikipedia.org/wiki/Caspase_11

1997). "CASH, a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641-4. doi:10.1074/jbc.272.32. ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis ... Wang, J; Chun H J; Wong W; Spencer D M; Lenardo M J (November 2001). "Caspase-10 is an initiator caspase in death receptor ...

https://en.wikipedia.org/wiki/Caspase_10

... a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proc. Natl. Acad ... Caspase-8 has been shown to interact with: BCAP31, BID, Bcl-2, CFLAR, Caspase-10, Caspase-2, Caspase-3, Caspase-6, Caspase-7, ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...

https://en.wikipedia.org/wiki/Caspase_8

Initiator caspases: responsible for the activation of effector caspases. These caspases are activated through oligomerization ... Structure: Death Effector Domain (DED) and a Caspase Recruitment Domain (CARD) that are englobed in a structure called pro- ... There are two groups of proteases: Effector caspases: induce the biggest part of the morphological changes that occur during ... Singh, Nitu; Hassan, Ali; Bose, Kakoli (2015). "Molecular basis of death effector domain chain assembly and its role in caspase ...

https://en.wikipedia.org/wiki/Death_effector_domain

... coli effector protein NleF is a caspase inhibitor". PLOS ONE. 8 (3): e58937. Bibcode:2013PLoSO...858937B. doi:10.1371/journal. ... Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other ... Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating ... Different protein isoforms of caspase-9 are produced due to alternative splicing. Similar to other caspases, caspase-9 has ...

https://en.wikipedia.org/wiki/Caspase-9

His highest cited papers are "Conversion of Bcl-2 to a Bax-like death effector by caspases", at 1332 times, and "Restoration of ... Conversion of Bcl-2 to a Bax-like death effector by caspases. 278:5345. Science. 1997 Andrea Ventura, David G Kirsch, Margaret ...

https://en.wikipedia.org/wiki/David_Kirsch

There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ... each leading to the activation of caspase-9. The nucleus and Golgi apparatus are other organelles that have damage sensors, ...

https://en.wikipedia.org/wiki/Neurodegenerative_disease

Death effector domain (DED): allows protein-protein binding by homotypic interactions (DED-DED). Caspase proteases trigger ... Pro-caspase-8 and pro-caspase-9 bind to specific adaptor molecules via DED domains, which leads to autoactivation of caspases. ...

https://en.wikipedia.org/wiki/Protein_domain

... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... Moon HS, Yang JS (February 2006). "Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells". Molecules ... In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also ... "Mitochondrial release of caspase-2 and -9 during the apoptotic process". The Journal of Experimental Medicine. 189 (2): 381-94 ...

https://en.wikipedia.org/wiki/AIFM1

The mitochondrial AIF protein was found to be a caspase-independent death effector that can allow independent nuclei to undergo ... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... Apoptosis inducing factor is involved in initiating a caspase-independent pathway of apoptosis (positive intrinsic regulator of ...

https://en.wikipedia.org/wiki/Apoptosis-inducing_factor

... coli Effector Protein NleF Is a Caspase Inhibitor". PLOS ONE. 8 (3): e58937. Bibcode:2013PLoSO...858937B. doi:10.1371/journal. ... Several bacterial effectors affect NF-kB signaling. For instance, the EPEC/EHEC effectors NleE, NleB, NleC, NleH, and Tir are ... For instance, the EPEC/EHEC effectors NleH and NleF block apoptosis. Similarly, the Shigella effectors IpgD and OspG (a homolog ... In contrast to inhibition of apoptosis, several effectors appear to induce programmed cell death. For instance, EHEC effectors ...

https://en.wikipedia.org/wiki/Bacterial_effector_protein

In Drosophila melanogaster cells, caspase Dronc is ubiquitylated by Diap-1. Similarly, effector caspases Caspase-3 and Caspase- ... In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ... Nedd2-like caspase is responsible for the activation of effector caspases. On the other hand, as a caspase, Dronc is fully ... Dronc can also be cleaved by the effector caspase DrICE, which is activated by caspase Dronc itself after autocleavage. However ...

https://en.wikipedia.org/wiki/Death_regulator_Nedd2-like_caspase

Death effector domain (DED) DEDs are present on caspases and are involved in caspase activation. DED-containing caspases ... Examples of death fold domains include the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), ... The motifs consist of several defined protein interactions with other suspected apoptotic roles (Lahm). Caspase recruitment ...

https://en.wikipedia.org/wiki/Death_fold

... the apoptotic effector caspase, caspase 3, cleaves ICAD and thus causes CAD to become activated. CAD cleaves the DNA at the ... The enzyme responsible for apoptotic DNA fragmentation is the Caspase-activated DNase. CAD is normally inhibited by another ... "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Nature. 391 (6662): 43-50. Bibcode: ... protein, the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, ...

https://en.wikipedia.org/wiki/DNA_fragmentation

... the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, the apoptotic effector caspase, caspase-3, cleaves ICAD and ... Caspase-activated DNase DNA laddering Sakahira, H; Enari, M; Nagata, S (January 1998). "Cleavage of CAD inhibitor in CAD ... When cells are induced to undergo apoptosis, caspase 3 cleaves ICAD to dissociate the CAD:ICAD complex, allowing CAD to cleave ... Cells that lack ICAD or that express caspase-resistant mutant ICAD thus do not show DNA fragmentation during apoptosis, ...

https://en.wikipedia.org/wiki/Apoptotic_DNA_fragmentation

... a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proceedings of ... Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ... As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after ... Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ...

https://en.wikipedia.org/wiki/Caspase_3

"P2X7 receptor-dependent blebbing and the activation of Rho-effector kinases, caspases, and IL-1 beta release". Journal of ...

https://en.wikipedia.org/wiki/P2RX7

... caspase-8-independent cell death pathway using the kinase RIP as effector molecule". Nature Immunology. 1 (6): 489-495. doi: ... is an alias for caspase-8). They elucidated the molecular mechanisms of caspase-8's involvement in cell death processes and in ... In 2000 he with 9 co-workers published their discovery "that, similar to apoptosis, caspase-independent cell death (necroptosis ... "viral and mammalian forms of the caspase-8-related protein FLIP" (FLICE-Like Inhibitory Protein, where "FLICE" ...

https://en.wikipedia.org/wiki/Jürg_Tschopp

It also selectively inhibits effector caspases 2, 3, 6, and 7 but not caspases 8 and 10. This compound has been shown to block ...

https://en.wikipedia.org/wiki/Z-FA-FMK

"Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain". The Journal of ... via the caspase-3 route). The role of Hip-1 in caspase mediated cell death remains unclear. Huntingtin interacting protein 1 ( ... It is known to contain a domain homologous to the death effector domains (DED) found on proteins involved in apoptosis. It is ... HIP1's pro apoptotic effect may involve activation of caspase-8 and a novel HIP1 protein interactor HIPPI. HIP1's non- ...

https://en.wikipedia.org/wiki/Huntingtin-interacting_protein_1

Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases ... 1] Apoptosis, Trail & Caspase 8 - The Proteolysis Map-animation PDB: 1D2Q TRAIL+Protein at the US National Library of Medicine ... TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. ... Feb 2016 Song JJ, Lee YJ (May 2008). "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation ...

https://en.wikipedia.org/wiki/TRAIL

Reduction of potassium ions promotes apoptosis and the synthesis of initiator caspase-8 and the effector caspase-3. A study ... that while caspase may play a role in apoptosis, it is specifically not as a result of caspase-3. It was reported in that study ... Caspase I is involved in the aforementioned cell membrane activity but not caspase-3. The sequence of events that leads to ... There are also differences in the initiation of mitochondrial (internal) and caspase-dependent (external) apoptosis for the UVC ...

https://en.wikipedia.org/wiki/UVB-induced_apoptosis

... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ... In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been ... This functional apoptosome then can provide a platform activation of caspase 9. Caspase 9 exists as a zymogen in the cytosol ... In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ...

https://en.wikipedia.org/wiki/Apoptosome

... has been shown to interact with: Caspase 8, FADD, and MAPK1, Phospholipase D1, and RPS6KA3. GRCh38: Ensembl release 89: ... PEA15 is a death effector domain (DED)-containing protein predominantly expressed in the central nervous system, particularly ... "Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha ... "Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha ...

https://en.wikipedia.org/wiki/PEA15

This positive feedback exerts an auto-activation of the effector caspase by means of intermediate caspases. When isolated from ... regardless of the number of intermediate activation steps of the effector caspase. When this core process is complemented with ... Apoptosis is a caspase-mediated process of cellular death, whose aim is the removal of long-lived or damaged cells. A failure ... The very core of the apoptotic process is the auto-activation of caspases, which may be modeled via a positive-feedback loop. ...

https://en.wikipedia.org/wiki/Positive_feedback

Procaspase 8 binds to FADD's death effector domain (DED) and proteolytically self-activates as caspase 8. Fas, FADD, and ... The AICD effector cell is one that expresses FasL, and apoptosis is induced in the cell expressing the Fas receptor. Both ... Apoptosis Immune system Immune tolerance T-cell Autoimmunity Fas receptor Caspase Zhang J, Xu X, Liu Y. (2004), Activation- ... However, overexpression of the protein CFLAR (caspase and FADD-like apoptosis regulator) inhibits Fas-mediated apoptosis. ...

https://en.wikipedia.org/wiki/Activation-induced_cell_death

A high concentration of caspase-8 induces its autoproteolytic activation and subsequent cleaving of effector caspases, leading ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. ...

https://en.wikipedia.org/wiki/Tumor_necrosis_factor

... two-hybrid screening using constitutive-active caspase-7 as bait in the identification of PA28gamma as an effector caspase ...

https://en.wikipedia.org/wiki/PSME3

It can also regulate the activities of both caspase-1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB ... Information from many literature sources indicates that an N-terminal pyrin effector domain (PYD) is one of the components of ... The NALP2 protein has a role in the activation process of caspase-1, which is encoded as CASP1; MIM 147678. The activation ... The NALP2 may also take part in protein complexes, which initiates the activation of proinflammatory caspases. NLR family ...

https://en.wikipedia.org/wiki/NLRP2

Jun JI, Chung CW, Lee HJ, Pyo JO, Lee KN, Kim NS, Kim YS, Yoo HS, Lee TH, Kim E, Jung YK (2005). "Role of FLASH in caspase-8- ... This protein is highly similar to FLASH, a mouse apoptotic protein identified by its interaction with the death-effector domain ... DED) of caspase 8. Researches of FLASH protein suggested that this protein may be a component of the death-inducing signaling ... "The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis". Nature. 398 (6730): ...

https://en.wikipedia.org/wiki/CASP8AP2

HAVCR2/ galectin-9 interaction attenuated T-cell expansion and effectors function in tumor microenvironment and chronic ... "Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ...

https://en.wikipedia.org/wiki/Galectin-9

Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid ...

https://en.wikipedia.org/wiki/TRADD

... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... The NBS-LRR proteins are required for effector triggered immunity (ETI). PRRs commonly associate with or contain members of a ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ...

https://en.wikipedia.org/wiki/Pattern_recognition_receptor

In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator ... vital functions of apoptotic effectors". Cell Death and Differentiation. 15 (7): 1113-23. doi:10.1038/cdd.2008.28. PMC 2917777 ... Lemarié A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L (Jun 2004). "Cadmium induces caspase-independent ... This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the ...

https://en.wikipedia.org/wiki/ENDOG

2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... Second, the activated G-protein produces a primary effector. Third, the primary effect stimulates the second messenger ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... The G-protein coupled receptors for the PIP2 messenger system produces two effectors, phospholipase C (PLC) and ...

https://en.wikipedia.org/wiki/Lipid_signaling

In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the other the complex ... Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming death-inducing signaling complex ( ... which then causes the activation of effector caspase. The latter mechanism is the focus of many oncogenic therapies because p53 ... In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase-independent manner; however, there is still ...

https://en.wikipedia.org/wiki/Anticancer_gene

An effector of the TGFbeta receptor, Smad3, may interact directly with APC subunit APC10 and thus recruit the APC complex. CDH1 ... NEDD9 is subject to both caspase cleavage and proteasomal degradation. In conditions of cell detachment, and particularly in ... A number of studies have identified NEDD9 as a downstream effector in the TGF-beta signaling pathway, essential for promoting ... Nedd9 interacts directly with the EGFR effector protein Shc, positioning it to affect downstream signaling relevant to EGFR; ...

https://en.wikipedia.org/wiki/NEDD9

HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... Plants also carry immune receptors that recognize variable pathogen effectors. These include the NBS-LRR class of proteins. ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ...

https://en.wikipedia.org/wiki/Innate_immune_system

Kleaiter N, Hermann; Baier, Gottfried (2010). "NFAT pulls the strings during CD4+ T helper cell effector functions". Blood. 115 ... are directly responsible for the expression of anergy associated genes such as ubiquitin ligase GRAIL or a protease caspase 3. ...

https://en.wikipedia.org/wiki/Clonal_anergy

Schwarz-Romond, T. (2005). "The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable ... The AIM2 and NLRP3 inflammasomes are filamentous assemblies that elicit host defense inside cells by activating caspase-1 for ...

https://en.wikipedia.org/wiki/Signalosome

"Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ". Blood. 98 (7): 2143-2151. doi: ... "Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ...

https://en.wikipedia.org/wiki/Epigenetics_of_neurodegenerative_diseases

Caspases are part of the apoptosis pathway. When BCl-2 decreases, the expression of caspases increases. As a result, apoptosis ... Organic carbon sources stimulate C-PC synthesis in Anabaena spp., but seem to have almost no effector negative effect in A. ...

https://en.wikipedia.org/wiki/Phycocyanin

Active caspase-8 is then released from the DISC into the cytosol, where it cleaves other effector caspases, eventually leading ... FADD also contains a death effector domain (DED) near its amino terminus, which facilitates binding to the DED of FADD-like ICE ... In most cell types, caspase-8 catalyzes the cleavage of the pro-apoptotic BH3-only protein Bid into its truncated form, tBid. ... FLICE), more commonly referred to as caspase-8. FLICE can then self-activate through proteolytic cleavage into p10 and p18 ...

https://en.wikipedia.org/wiki/Fas_ligand

It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis. GRASP65 can ... Short B, Preisinger C, Körner R, Kopajtich R, Byron O, Barr FA (December 2001). "A GRASP55-rab2 effector complex linking Golgi ... Lane JD, Lucocq J, Pryde J, Barr FA, Woodman PG, Allan VJ, Lowe M (2002). "Caspase-mediated cleavage of the stacking protein ... Cheng JP, Betin VM, Weir H, Shelmani GM, Moss DK, Lane JD (2010). "Caspase cleavage of the Golgi stacking factor GRASP65 is ...

https://en.wikipedia.org/wiki/GRASP65

... also does not bind to active caspase-8. Caspase-3 and -7 are effector proteases whereas caspase-8 is an initiator ... The human IAPs, XIAP, c-IAPl, C-IAP2 have been shown to bind to caspase-3 and -7, which are the effector caspases in the ... which recruits activator caspases like caspase-8 upon binding TNF at the cell surface. The activation of the initiator caspases ... Active caspase-3 and -7 coimmunoprecipitated with survivin. The inactive proforms of caspase-3 and -7 did not bind survivin. ...

https://en.wikipedia.org/wiki/Survivin

Other roles include cytokine production (Il-4,IL-9) to help recruit other effector cells of the immune response. According to ... These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis. Giardia protects its own ...

https://en.wikipedia.org/wiki/Giardiasis

... has been shown to interact with Caspase 8. GRCh38: Ensembl release 89: ENSG00000114446 - Ensembl, May 2017 GRCm38: ... crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ...

https://en.wikipedia.org/wiki/IFT57

Joneson T, Bar-Sagi D (1997). "Ras effectors and their role in mitogenesis and oncogenesis". J. Mol. Med. 75 (8): 587-93. doi: ... 2006). "Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL". Hum. Mol. ...

https://en.wikipedia.org/wiki/MAPK13

2007). "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway". EMBO J. 26 ( ... which suggests a role for this gene as an effector of p53-dependent apoptosis. Three alternatively spliced transcript variants ... 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 ...

https://en.wikipedia.org/wiki/LRDD

There are four types of death domain subfamilies: death effector domain (DED), caspase recruitment domain (CARD), pyrin domain ... DED: Death effector domain, retrieved 3 November 2016 Reed, JC; Doctor, KS; Godsik, A (2004). "The domains of apoptosis: A ... CARD: Caspase recruitment domain, retrieved 3 November 2016 Bouchier-Hayes, L; Martin, SJ (2002). "CARD games in apoptosis and ... DDs can also be found with other types of domains including Ankyrin repeats, caspase-like folds, kinase domains, leucine ...

https://en.wikipedia.org/wiki/Death_Domain_database

As the reservoir of growth factors is removed the endothelial cells do not survive, and undergo caspases induced apoptosis, ... 2004). "Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis". Cancer ...

https://en.wikipedia.org/wiki/Proteases_in_angiogenesis

Caspase 2: caspase 2, apoptosis-related cysteine peptidase [4][permanent dead link] Caspase 4: caspase 4, apoptosis-related ... Other motifs in this class include the pyrin domain (PYD), death domain (DD), and death effector domain (DED), all of which ... Caspase 9: caspase 9, apoptosis-related cysteine peptidase [7][permanent dead link] Caspase 12: caspase 12, apoptosis-related ... caspase 13, apoptosis-related cysteine peptidase [9] ICEBERG: caspase 1 inhibitor iceberg [10] Pseudo-ICE:Caspase-1 dominant- ...

https://en.wikipedia.org/wiki/CARD_domain

These T cells can then go on to perform effector functions such as macrophage activation, B cell activation, and cell-mediated ... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ...

https://en.wikipedia.org/wiki/Autocrine_signaling

Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are ... Furthermore, the study showed midiv-1 was capable to preventing the activation of caspase 3 by reversing the release of ... Lackner LL, Horner JS, Nunnari J (August 2009). "Mechanistic analysis of a dynamin effector". Science. 325 (5942): 874-7. doi: ... Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC (March 2003). "Caspase cleavage product of BAP31 induces mitochondrial ...

https://en.wikipedia.org/wiki/DNM1L

... caspase-1, -4, -5 and -11) and as an effector molecule for the lytic and highly inflammatory form of programmed cell death ... Cardiolipin Pyroptosis Inflammasome GSDMA GSDMB GSDMC DFNA5 Caspases Caspase-1 Caspase-4 Caspase-5 Caspase-11 Interleukin-1β ... Caspase-11 in mice and its human homolog caspase-4 and -5 are involved in the non-canonical pathway and are activated by ... Caspase-1, conserved in vertebrates, is involved in the canonical pathway and is activated by canonical inflammasomes such as ...

https://en.wikipedia.org/wiki/GSDMD

... to inhibit their caspase-binding activity and allow for caspase activation of apoptosis. SMAC is ubiquitously expressed in many ... vital functions of apoptotic effectors". Cell Death and Differentiation. 15 (7): 1113-23. doi:10.1038/cdd.2008.28. PMC 2917777 ... "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature. 410 (6824): ... Du C, Fang M, Li Y, Li L, Wang X (2000). "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation ...

https://en.wikipedia.org/wiki/Diablo_homolog

Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which ... Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3. Science, 330(6002), pp. 390-393. (doi: 10.1126/ ... The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger ... During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an ...

http://eprints.gla.ac.uk/43838/

Fig.3),3), which prominently features the 3-pyrrolidine-2-yl-pyridine nucleus in enantiopure form (24). pathology of tobacco abuse. The reaction between reducing sugars and amines, known as the Maillard reaction, was first described 90 years ago (1). Also termed nonenzymatic browning, the Maillard reaction has been extensively reviewed by food chemists for its part in the development and deterioration of flavor and the effects within the nutritional value of foods during processing and storage (2, 3). In the past 20 years, the Maillard reaction has attained unique prominence biologically because of its part in certain disease claims including diabetes (4), malignancy (5), atherosclerosis (6), and Alzheimers disease (7, 8), as well as normal ageing (9). The initial step in this process entails the reversible formation of a Schiff foundation between an amine and the ring-opened form of a reducing sugars, followed by Amadori rearrangement to give deoxyglucosones (Fig. ?(Fig.11of ...

http://rmrfotoarts.com/fig/

... and caspase activation in WGA-treated in HeLa, SiHa, and CaSKi cells. Additionally, we examined the part of Alfy within the ER ... PD-1 suppresses T-cell proliferation and activation and dampens the function of effector T cells.80 PD-1 can be highly ...

http://rmrfotoarts.com/category/pkd/

This could be explained by a much higher uptake of these MSNs from the cells (Figure S3).The results show that all the produced MSNs are biocompatible at concentrations Etamivan as high as 50 g/mL. malignancy, and inflammation, shown enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs therefore remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug focusing on and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI covering exhibiting higher affinity for the small intestine and PEICPEG covering for the colon. The data highlight the potential of nanomedicines for targeted delivery to unique regions of the cells for strict restorative control. Keywords: intestinal focusing on, PEG-PEI copolymer, Notch inhibition Intro Targeting specific biological pathways Hyal2 provides an opportunity to devise more specific and more effective approaches in malignancy and ...

https://rmrfotoarts.com/category/p75/

XIAP, which binds to the active site of all of the main effector caspases (caspase-3, -7, and -9), is known to prevent ... Effector Caspase Inhibition to Prevent Both Extrinsic and Intrinsic Signals. Based on the studies cited above, it has become ... multiple effector caspases late in the cascade of apoptotic triggers, thus preventing cell death at one common point for a ...

https://www.medscape.com/viewarticle/540528_3

Caspases, Effector/antagonists & inhibitors. Caspase Inhibitors. Caspases, Initiator/antagonists & inhibitors. Caspase ... Caspase Inhibitors. Caspase 2/antagonists & inhibitors. Caspase Inhibitors. Caspase 3/antagonists & inhibitors. Caspase ... Caspase Inhibitors. Caspase 7/antagonists & inhibitors. Caspase Inhibitors. Caspase 8/antagonists & inhibitors. Caspase ... Caspase Inhibitors. Caspase 10/antagonists & inhibitors. Caspase Inhibitors. Caspase 12/antagonists & inhibitors. Caspase ...

https://www.nlm.nih.gov/pubs/techbull/nd12/nd12_entry_combo_table.html

Small-molecule XIAP inhibitors derepress downstream effector caspases. Toggle navigation AIM: To recognize risk factors ...

http://rmrfotoarts.com/aim-to-recognize-risk-factors-associated-with-survival-in-patients-retransplanted/

... and caspase 9), followed by activation of caspase 9, which in turn cleaves downstream effector caspases 3, 6, and 7; Smac/ ... The caspase cascade. The caspase cascade acts as the principal executioner in apoptosis (4-6). Caspases are synthesized as ... The latter can be further grouped as initiators (caspases 2, 8, 9, and 10) and effectors (caspases 3, 6, and 7). Once switched ... Caspase 8 stimulation in type I cells is sufficient to activate effector caspases and commit the cell to apoptotic death. In ...

https://www.jci.org/articles/view/34359

Thus, we show that the V. cholerae El Tor biotype does not trigger caspase-11 activation, but instead triggers parallel Nlrp3- ... Thus, we show that the V. cholerae El Tor biotype does not trigger caspase-11 activation, but i... ... we here show that El Tor Vibrio cholerae induces IL-1β maturation and secretion in a caspase-11- and CT-independent manner. ... we here show that El Tor Vibrio cholerae induces IL-1β maturation and secretion in a caspase-11- and CT-independent manner. ...

https://www.frontiersin.org/articles/10.3389/fimmu.2019.02463/full

... where initiator caspases (i.e., caspases-8, and -10) function to cleave effector caspases (i.e., caspases-3 and -7), which in ... XIAP, which binds to the active site of all of the main effector caspases (caspase-3, -7, and -9), is known to prevent ... Caspase-8 associates with the DISC complex, where it is activated and released, leading to effector caspase activation (notably ... preventing the activation of caspase-8 and its ability to activate downstream effector caspases (Fig. 2). ...

https://diabetesjournals.org/diabetes/article/55/7/1907/14101/Interventional-Strategies-to-Prevent-Cell

Active caspase 8 cleaves and activates downstream effector caspases, such as caspases 3 and 7. Effector caspases cleave ... causing the activation of caspase 9 [5,8]. Active caspase 9 goes on to activate effector caspases and the apoptosis inducing ... One effector caspase commonly utilized in the intrinsic pathway is caspase 3. Studies in our laboratory using genetic analysis ... 2.1 Caspases. Multiple studies demonstrate that HDAP is caspase-dependent [19,23,47-50]. The small peptide pan-caspase ...

https://www.mdpi.com/1999-4915/1/3/965/htm

The central effectors of cell death in the immune system. Annu. Rev. Immunol. 17:781. ... The differential induction of caspase-1 in SW480 and SW620 cells by IFN-γ indicated that caspase-1 might have mechanistically ... revealed that caspases-1 and -7 were up-regulated by IFN-γ in SW480 cells and caspase-7 in SW620 cells. RT-PCR analysis also ... and then recultured in the absence or presence of peptide-based caspase inhibitors with specificity for caspase-1, Z-YVAD-FMK, ...

https://www.jimmunol.org/content/170/12/6329

Active caspase-9 directly cleaves and activates the effector protease, caspase-3. The apoptotic pathway induced by Cd2+ is ... 2000). In the present study, Cd2+ induced caspase-3, caspase-8, and caspase-9 activation. In addition, caspase-3 inhibitor (Z- ... The caspase inhibitorsfor caspase-3 and caspase-9, in particular, inhibited Cd2+-induced cell death (Figure 5A).The caspase-3 ... Assay of caspase activity. The enzymatic activity of caspase was assayed using a caspase colorimetric assay kit (R&D Systems) ...

https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.10467

... antiviral effectors (e.g., IFI44, Viperin and SAMHD-1) and proteins involved in the apoptosis (e.g., TNF and caspase-3) and ...

https://www.nature.com/articles/s41467-018-06659-3

... like caspase-8 and caspase-9, whose role is to activate the other caspases, and the effector or downstream caspases, like ... Caspase-3 degrades its substrates such as ICAD/DFF45, an inhibitor of the endonuclease CAD/DFF40 (caspase associated DNAse), ... Caspases involved in apoptosis could be classified in 2 groups: the initiator or apical caspases, ... These proteases are called caspases, cysteinyl aspartic acid proteases [21]. Caspases are produced as proenzymes which must be ...

https://www.hindawi.com/journals/ijr/2011/495792/

Caspase-1. Caspase-1 initiates immune resopnses by cleaving and activating key downstream effector proteins. Cells express ... In the course of our work on the innate immune system, we have uncovered several examples of effector-triggered immunity and ... Once assembled, inflammasomes serve as a scaffold for the dimerization and activation of inflammatory caspases, most notably, ... One alternate mechanism, sometimes called Effector-triggered Immunity, proposes that hosts might not only detect pathogen ...

https://mcb.berkeley.edu/faculty/imp/vancer.html

Here, we demonstrate an essential role for an effector caspase in the activation of compensatory ... Hsp83 loss suppresses proteasomal activity resulting in an upregulation of caspase-dependent compensatory autophagy. ...

https://www.sigmaaldrich.com/US/en/search/p3813?focus=papers&page=1&perpage=30&sort=relevance&term=p3813&type=citation_search

... to a method of monitoring and/or modulating disease-associated activatory procceses which are mediated by caspase-10 or caspase ... The death effector domain (DED) of FADD in turn interacts with the DED of pro-caspase-8 and thereby recruits this proenzyme to ... The blots were probed for Caspase-10, showing recruitment of caspase-10 in caspase-8 deficient cell line 1D2 and in the caspase ... FLICE-2 as caspase-10b, and the two recently identified variants as caspase-10c and caspase-10d. While the caspase-10a, -10b ...

https://www.freepatentsonline.com/y2006/0240422.html

... effector caspase-3/7 activation; (e-1) IL-1β and IL-18 activation from pro- IL1β and pro-IL18 inactive form by caspase-1; (e-2 ... cleavage of pro-caspase-9 N-terminal region (inactive form) by the apoptosome molecular complex; (C) caspase-8/10 activaton by ... Scheme of caspase - 1/3/7 activation mediated by inflammasome and/or apoptosome. (a-1) initiation of NLRP3 oligomerization (by ... Scheme of caspase - 1/3/7 activation mediated by inflammasome and/or apoptosome. (a-1) initiation… ...

https://pubmed.ncbi.nlm.nih.gov/33603750/

... caspase-3 and caspase-9, are also described. We conclude with a brief analysis of the potential therapeutic options arising ... and the effector caspases, which are activated by the executioner caspases.. In a resting cell, caspases are present as ... Caspase-8 and c-FLICE (caspase-8) inhibitory protein. Caspase-8 is the key initiator caspase downstream of the apoptosis ... caspase-8) inhibitory protein, is structurally similar to caspase-8 in that it possesses death effector domains and a caspase- ...

https://arthritis-research.biomedcentral.com/articles/10.1186/ar569

Conversely, caspase-1 was necessary for NOS2 expression, but dispensable for NF-κB activation, indicating that this protease ... Remarkably, caspase-1-mediated Nos2 transcription and NO production contribute to the resistance of macrophages to Salmonella ... We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and ... We demonstrated that epigenetic regulation of Nos2 by caspase-1 involves cleavage of the chromatin regulator PARP1 (also known ...

https://www.nature.com/articles/srep41686?error=cookies_not_supported&code=c926e6f4-e46f-441c-858a-34480262550f

Beyond effector caspase inhibition: Bcl2L12 neutralizes p53 signaling in glioblastoma. Stegh AH, DePinho RA. Stegh AH, et al. ...

https://www.ncbi.nlm.nih.gov/pubmed/23901115

Serial killers: ordering caspase activation events in apoptosis. Slee, E. A., Adrain, C. & Martin, S. J., Nov 1999, In: Cell ...

https://pure.qub.ac.uk/en/organisations/school-of-biological-sciences/publications/?ordering=publicationYearThenTitle&descending=true&page=147

HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic caspase-8 effector ... Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN ... enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased ... All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with ...

http://www.cancerindex.org/geneweb/TNFRSF1A.htm

PARP-1 knockdown in HL-60 cells confirmed that PARP-1 participates in effector caspase activation. Finally, PJ-34 also ... suggesting that PARP-1 participates in caspase-dependent apoptosis. Indeed, PARP-1 inhibition reduced TGHQ-induced caspase-3, - ... Intriguingly, although z-vad-fmk (a pan-caspase inhibitor) attenuated TGHQ-induced apoptosis, cotreatment with PJ-34 led to a ... In contrast, PJ-34 potentiated TGHQ-induced caspase-8 activation, suggesting that PARP-1 plays a dual role in regulating TGHQ- ...

https://tools.niehs.nih.gov/portfolio/index.cfm?do=portfolio.publicationDetail&id=1897830

Apoptosis in response to cellular stress such as treatment with cytotoxic drugs is mediated by effector caspases (caspase-3) ... Apoptosis in response to cellular stress such as treatment with cytotoxic drugs is mediated by effector caspases (caspase-3) ... In these cells, caspases including caspase-8 were activated by mitochondria-driven signaling events and no DISC was detected ... In these cells, caspases including caspase-8 were activated by mitochondria-driven signaling events and no DISC was detected ...

https://www.unboundmedicine.com/medline/citation/11314043/Cell_type_specific_involvement_of_death_receptor_and_mitochondrial_pathways_in_drug_induced_apoptosis_

SOLUTION STRUCTURE OF THE CASPASE RECRUITMENT DOMAIN (CARD) FROM APAF-1 ... but is coincident with that of the structurally similar FADD death effector domain and the Apaf-1 CARD interface identified by ... Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1.. Day, C.L., Dupont, C., Lackmann, M., ... SOLUTION STRUCTURE OF THE CASPASE RECRUITMENT DOMAIN (CARD) FROM APAF-1. *PDB DOI: 10.2210/pdb1CWW/pdb ...

https://www.rcsb.org/structure/1cww

... coli stimulates effector-driven rapid caspase-4 activation in human macrophages, Cell Reports, Vol:27, ISSN:2211-1247, Pages: ... Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death, Nature Communications, Vol:7, ... The atypical ubiquitin E2 conjugase UBE2L3 is an indirect caspase-1 target and controls IL-1beta secretion by inflammasomes, ... Human GBP1 differentially targets salmonella and toxoplasma to license recognition of microbial ligands and caspase-mediated ...

https://www.imperial.ac.uk/people/a.shenoy/?respub-action=citation.html&id=1107241&noscript=noscript

Caspases [D12.776.476.075.405] * Caspases, Effector [D12.776.476.075.405.350] * Caspase 3 [D12.776.476.075.405.350.300] ... Caspases [D08.811.277.656.262.500.126] * Caspases, Effector [D08.811.277.656.262.500.126.350] * Caspase 3 [D08.811.277.656. ... Caspases [D08.811.277.656.300.200.126] * Caspases, Effector [D08.811.277.656.300.200.126.350] * Caspase 3 [D08.811.277.656. ... Caspases, Effector Preferred Concept UI. M0491613. Registry Number. EC 3.4.22.-. Scope Note. A subclass of caspases that ...

https://meshb.nlm.nih.gov/record/ui?ui=D053470

Caspases play an essential role in the apoptosis, necrosis and inflammation processes. (intechopen.com)
As of now, at lease 14 caspases have been described from mammals: 8 caspases are involved in apoptosis, 5 activate anti-inflammatory cytokines, and one acts in keratinocyte differentiation. (intechopen.com)
During apoptosis, different caspases perform different functions. (intechopen.com)
Long-term depression, a proposed physiological correlate of synapse elimination, requires caspase-3 and the mitochondrial pathway of apoptosis. (jneurosci.org)
However, pharmacological inhibition of inhibitor of apoptosis proteins or proteasome function led to neuronal death, suggesting that caspase activation is spatially restricted by these "molecular brakes" on apoptosis. (jneurosci.org)
Activation of caspase-3, an executioner caspase that lies downstream of both extrinsic and intrinsic (mitochondrial) pathways of apoptosis, plays a central role in programmed cell death of many cell types, including neurons ( Fuchs and Steller, 2011 ). (jneurosci.org)
Recent studies, however, have established that the molecular mechanisms of apoptosis, including caspases, are also involved in nonapoptotic functions ( Hyman and Yuan, 2012 ). (jneurosci.org)
Until now, there has been no direct demonstration that local activation of caspase-3 can alter synapse function and morphology without causing apoptosis. (jneurosci.org)
Local activation of the mitochondrial apoptosis pathway in dendrites is sufficient to cause elimination of spines and dendrite branches that are localized in the vicinity of Mito-KillerRed photostimulation in a manner dependent on caspase-3 activation. (jneurosci.org)
We present evidence that the restriction of caspase-3 activation to the region of photostimulation-and hence protection against cell death-is mediated by the action of proteasomes and the inhibitor of apoptosis proteins (IAPs). (jneurosci.org)
Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. (nih.gov)
This article reviews these latest advances and describes our present understanding of caspase regulation during apoptosis. (nih.gov)
Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or caspase 10. (reading.ac.uk)
These caspases are responsible for the cleavage of the key cellular proteins, such as cytoskeletal proteins, that leads to the typical morphological changes observed in cells undergoing apoptosis. (reading.ac.uk)
The mitochondria are also key regulators of the caspase cascade and apoptosis. (reading.ac.uk)
During apoptosis, ICAD is cleaved by caspases, such as caspase 3, to release CAD. (reading.ac.uk)
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). (genome.jp)
Caspase-3 Inhibitors offered by Santa Cruz inhibit caspase-3 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
The inhibitor of apoptosis proteins (IAPs) plays a central role in repressing caspase-mediated cell death. (aacrjournals.org)
[ 61 ] In addition, an ex vivo analysis of CD8 + CD28 − T lymphocytes showed increased expression of caspase-3 when compared with the CD8 + CD28 + T-cell subpopulation, suggesting a higher susceptibility of apoptosis in senescent lymphocytes. (medscape.com)
As mediated by the estrogen receptor, BPA may induce the pyroptosis of neuroblastoma cells through NLRP3/caspase-1/GSDMD signaling pathway, and caspase-1-dependent pyroptosis may be involved in BPA-induced apoptosis, which is alleviated by EGCG, an anti-oxidation agent. (researchsquare.com)
FLIP down-regulation as well as caspase-8 activation and apoptosis induced by FasL were all inhibited by the NO-liberating agent sodium nitroprusside and dipropylenetriamine NONOate, whereas the NO synthase inhibitor aminoguanidine and NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO) had opposite effects, indicating an anti-apoptotic role of NO in the Fas signaling process. (cdc.gov)
Abrogating mitochondrial cell death by genetic deletion of the effectors of intrinsic apoptosis, BAX, and BAK, or the regulator of mitochondrial permeability transition pore formation, cyclophilin-D, did not affect bacterial growth or the initial killing of macrophages. (wustl.edu)
They have two main roles within the apoptosis cascade: as initiators that trigger the cell death process, and as effectors of the process itself. (embl.de)
Caspase-mediated apoptosis follows two main pathways, one extrinsic and the other intrinsic or mitochondrial-mediated. (embl.de)
The subsequent activation of caspase-8 initiates the apoptosis cascade involving caspases 3, 4, 6, 7, 9 and 10. (embl.de)
The different caspases have different domain architectures depending upon where they fit into the apoptosis cascades, however they all carry the catalytic p10 and p20 subunits. (embl.de)
Caspases can have roles other than in apoptosis, such as caspase-1 (interleukin-1 beta convertase) ( EC 3.4.22.36 ), which is involved in the inflammatory process. (embl.de)
The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. (embl.de)
A short pro-domain caspase that plays an effector role in APOPTOSIS . (nih.gov)
Fenretinide induced high levels of caspase-dependent apoptosis accompanied by an increase in free radicals and the release of cytochrome c in the absence of mitochondrial permeability transition. (elsevier.com)
These results suggest that the effector pathway of fenretinide-induced apoptosis of neuroblastoma is caspase dependent, involving mitochondrial release of cytochrome c independently of permeability changes, and mediated by specific RARs. (elsevier.com)
Caspase-8 activity is regulated by CASP8 and FADD-like apoptosis regulator. (smpdb.ca)
Therefore, to maximize the therapeutic potential of magnetic hyperthermia for the treatment of cancer, there is a clear need to simultaneously target the multiple key downstream effectors of HSPs that promote cell survival and inhibit apoptosis following treatment. (cdc.gov)
ABL-N administration induced apoptosis of PC3 cells in a dose-dependent manner, along with the enhanced activity of caspases and increased Bax/Bcl-2 ratio. (cusabio.com)

Depending on the phase at which those proteins enter the apoptotic cascade one distinguishes initiator (apical) and effector (executioner) caspases. (intechopen.com)
The caspases are a family of proteins that are one of the main executors of the apoptotic process. (reading.ac.uk)
The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus. (reading.ac.uk)
The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. (reading.ac.uk)
Cell death is induced by both pathways through the activation of caspases, which are enzymes that degrade proteins. (news-medical.net)
Other proteins that are injected by Salmonella, such as SopA (see crystal structure) and those from other gut bacteria like E. coli and Shigella flexneri , also carry targets for caspase-3, demonstrating the broad significance of this finding. (umassmed.edu)
Caspase family members function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. (scbt.com)
The results showed that BPA nonlinearly upregulated the levels of IL-18, ASC, GSDMD and NLRP3 mRNAs and that of NLRP3, caspase-1, GSDMD and IL-1β proteins in IMR-32 and SK-N-SH cells. (researchsquare.com)
Meanwhile, Z-YVAD-FMK and ICI182.780 abruptly reduced the levels of Bak1, Bax, Bcl-2 and caspase-3 proteins induced by BPA. (researchsquare.com)
Stimulation of cell surface Fas (CD95) results in recruitment of cytoplasmic proteins and activation of caspase-8, which in turn activates downstream effector caspases leading to programmed cell death. (cdc.gov)
Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. (embl.de)
At the end of the cascade, caspases act on a variety of signal transduction proteins, cytoskeletal and nuclear proteins, chromatin-modifying proteins, DNA repair proteins and endonucleases that destroy the cell by disintegrating its contents, including its DNA. (embl.de)
Several families of proteins including the Bcl-2, tumor necrosis factor receptor 1, and caspase families play essential roles in the regulation, signaling, and execution of the genetic cell death program. (embl.de)
Once activated, caspases -3 and -7 cleave downstream proteins. (smpdb.ca)

Caspases are a family of cysteine-dependent aspartate specific proteases. (intechopen.com)
Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. (embl.de)
αII-Spectrin, a structural protein of the cell cytoskeleton with a molecular weight of 250 kDa, is a major substrate of cytosolic cysteine proteases, such as calpains and caspases [ 5 ]. (biomedcentral.com)
Caspases are are proteases that cleave their substrates. (smpdb.ca)

In H460 cells, the overexpressed XIAP, but not c-IAP1, bound to the processed form of caspase-9 and suppressed the activation of downstream effector caspases. (aacrjournals.org)

Santa Cruz Biotechnology now offers a broad range of caspase-3 Inhibitors. (scbt.com)
Here we review the literature on PIK3CA mutations in cancer, as well as existing data on p110α inhibitors and inhibitors of downstream effectors for potential use as targeted cancer therapeutics. (benthamscience.com)

There are two types of caspases: inhibitor caspases and executioner caspases (inhibitor caspases activate the executioner caspases). (news-medical.net)
View detailed caspase-3 Inhibitor specifications, including caspase-3 Inhibitor CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (scbt.com)
Q-VD-OPH is a low toxicity broad-spectrum inhibitor of caspase-3, caspase-1, caspase-8 and caspase-9. (scbt.com)
PKR Inhibitor inhibits RNA-induced PKR autophosphorylation, as well as caspase-3 and caspase-8, and prevents increases in pT(451)-PKR and pS(194)-FADD levels in SH-SY5Y nuclei. (scbt.com)
The presence of Ac-DEVD-CHO (a caspase-3 inhibitor) markedly enhanced the potency of TL04 in improving the viability of glutamate-exposed DPC12 cells. (spandidos-publications.com)
Free radical induction in response to fenretinide was not blocked by the caspase inhibitor ZVAD or by RAR antagonists and was only marginally reduced in cells selected for resistance to fenretinide. (elsevier.com)

These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. (genome.jp)
Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways. (umaryland.edu)

Granzyme B, similarly to the caspases, cleaves its substrates after aspartic acid residues, suggesting that this protease has the ability to activate members of the caspase family directly. (genome.jp)

The extrinsic, death receptor pathway triggers the activation of a caspase cascade, and the intrinsic, mitochondrial pathway shifts the balance in the Bcl-2 family towards the pro-apoptotic members, promoting the formation of the apoptosome, and consequently caspase-mediated apoptosis. (biologists.com)

Collectively, the results demonstrated that the purified polysaccharides separated from Tremella fuciformis (TL04) possess a neuroprotective effect against glutamate-induced DPC12 cell damage predominantly through the caspase-dependent mitochondrial pathway. (spandidos-publications.com)

This effect is mediated through the formation of an apoptosome, a multi-protein complex consisting of cytochrome C, Apaf-1, pro-caspase 9 and ATP. (reading.ac.uk)
We found that the cytochrome c /apoptotic protease-activating factor-1 (apoptosome)-dependent caspase activation is deficient in human non-small cell lung cancer (NSCLC) NCI-H460 cells. (aacrjournals.org)
The stimulation or inhibition of different Bcl-2 family receptors results in the leakage of cytochrome c from the mitochondria, and the formation of an apoptosome composed of cytochrome c, Apaf1 and caspase-9. (embl.de)

Initiator caspase activation is more sophisticated - by special protein complexes: apoptosomes, PIDDosomes, DISC ( death-inducing signalling complexes ) [ 7 , 8 ]. (intechopen.com)
RSF also activated caspase‑3 and -9 and regulated the activations of mitogen-activated protein kinases (MAPKs). (medsci.org)
The Salmonella effector protein SipA has amino acid motifs that are recognized by caspase-3, which cleaves the bacterial protein into active virulence effectors: one stimulates actin polymerization to help cell entry and the other induces inflammation. (umassmed.edu)
The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. (wustl.edu)
We characterized the major LPS structures from two different pathogens, modeled their binding to the surface receptors, systematically examined macrophage inflammatory responses to these LPS molecules, and surveyed the temporal differences in global protein secretion resulting from TLR4 and caspase 11 activation in macrophages using mass spectrometry (MS)-based quantitative proteomics. (umaryland.edu)
This integrated strategy, spanning functional activity assays, top-down structural elucidation of endotoxins, and secretome analysis of stimulated macrophages, allowed us to identify crucial differences in TLR4- and caspase 11-mediated protein secretion in response to two Gram-negative bacterial endotoxins. (umaryland.edu)
Global Characterization of Protein Secretion from Human Macrophages Following Non-canonical Caspase-4/5 Inflammasome Activation. (umaryland.edu)
The Brucella effector protein TcpB induces degradation of inflammatory caspases and thereby subverts non-canonical inflammasome activation in macrophages. (umaryland.edu)
Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. (smpdb.ca)

The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity. (unibas.ch)
Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. (springer.com)
Intracellularly, LPS is recognized by caspase 11 through the noncanonical inflammasome to induce pyroptosis-an inflammatory form of lytic cell death. (umaryland.edu)
While TLR4-mediated signaling perturbations result in secretion of cytokines and chemokines that help clear infection and facilitate adaptive immunity, caspase 11-mediated pyroptosis leads to the release of damage-associated molecular patterns and inflammatory mediators. (umaryland.edu)

Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. (smpdb.ca)

Experiments demonstrate that the reduction of mitochondrial membrane potential (MMP, Δψ m) leads to the release of cytochrome c (Cyto C), whose cytoplasmic localization initiates caspase-dependent apoptotic cell death. (spandidos-publications.com)
The identification of caspases as major regulators of apoptotic cell death in animals initiated a quest for homologous peptidases in other kingdoms. (rupress.org)

All caspases are originally inactive, but activated when needed by cleavage of a small fragment by initiator caspases. (intechopen.com)
The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3. (reading.ac.uk)
Glutamate, which is elevated in the cerebrospinal fluid of ALS patients, induced DNA fragmentation and caspase-3 cleavage in the spinal cord motor neurons. (greenmedinfo.com)

Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells. (reading.ac.uk)
Deletion analysis shows that the caspase-like domain of FLIP is a key target for S-nitrosylation by NO, and mutations of its cysteine 254 and cysteine 259 residues completely inhibit S-nitrosylation, leading to increased ubiquitination and proteasomal degradation of FLIP. (cdc.gov)

Effector caspases are activated downstream of mitochondria, and cleave several cellular targets to result in the characteristic apoptotic morphology. (elsevier.com)

These caspases can then activate other caspases in a cascade. (reading.ac.uk)
Granzyme B can be delivered into cells by cytotoxic T lymphocytes and is able to directly activate caspases 3, 7, 8 and 10. (reading.ac.uk)
Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES . (nih.gov)

Previous studies have used genetic or pharmacologic manipulations to investigate the functions of caspases in neurons and synapses but, by their nature, such approaches cannot address local actions of caspases within specific neuronal compartments or longitudinally follow the changes in the same neuron after caspase activation. (jneurosci.org)
Although general structural features are shared between the initiator and the effector caspases, their activation, inhibition and release of inhibition are differentially regulated. (nih.gov)
This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. (reading.ac.uk)
There are a number of other mechanisms, aside from activation of the death receptors, through which the caspase cascade can be activated. (reading.ac.uk)
Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. (reading.ac.uk)
These cytokines are also released from activated γδ T cells and jointly combine to initiate pro-inflammatory feedback loops that augment the production of IL-1β, IL-6, and IL-23 by antigen presenting cells (APC), leading to enhanced Th17 responses and continued γδ T cell activation of the effector phase. (springer.com)
Activation of caspases can be mediated by other caspase homologues. (embl.de)
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. (nih.gov)

The fragmentation of DNA into nucleosomal units - as seen in DNA laddering assays - is caused by an enzyme known as CAD, or caspase activated DNase. (reading.ac.uk)
Salmonella tricks the host into synthesizing and secreting the apoptotic enzyme caspase-3, diverting this host enzyme to its own use. (umassmed.edu)
Cells containing lower concentrations of chymotrypsin-like enzyme activity will retain a lower level of fluorescence compared to cells containing higher concentrations of this effector enzyme component. (immunochemistry.com)

To this end, we are interested in delivering lethal-7a miRNA (let-7a), which is known to be a tumor suppressor that inhibits malignant growth by targeting factors such as the BRCA family, RAS, IGF1R, and c-Myc, which overlap with a number of key downstream effectors of HSPs. (cdc.gov)

IGF-I binds to the IGF-I receptor (IGF-IR) in motor neurons and activates MAPK and the downstream effector of phosphatidylinositol 3-kinase (PI-3K) signaling, Akt. (greenmedinfo.com)

We further suggest that metacaspases and paracaspases, although sharing structural and mechanistic features with the metazoan caspases, form a distinct family of clan CD cysteine peptidases. (rupress.org)

Biochemical and structural studies have led to important advances in understanding the underlying molecular mechanisms of caspase regulation. (nih.gov)

This concept also implies the existence of mechanisms that limit the activity of caspase-3 and prevent complete destruction of the cell. (jneurosci.org)

If the caspase motif contains a single-point mutation, then virulence is lost in mouse models of infection. (umassmed.edu)
Salmonella effectors: important players modulating host cell function during infection. (umassmed.edu)
[ 62 ] In studies of experimental models, Nikolich-Zugich's group showed that CMV infection causes marked changes in the CD8 + T cell pool, namely an increase in this pool and a distorted TCR repertoire diversity, due to expansion of the memory effector cell subpopulation concomitant to a reduced naive subpopulation. (medscape.com)

Caspases are synthesized as inactive pro-caspases. (smpdb.ca)

FLISP may be used in combination with FLICA to discriminate serine protease activity from caspase activity in the same cell. (immunochemistry.com)

Here, we show that caspase-3 activity is essential-and can act locally within neurons-for regulation of spine density and dendrite morphology. (jneurosci.org)
By photostimulation of Mito-KillerRed, we induced caspase-3 activity in defined dendritic regions of cultured neurons. (jneurosci.org)
However, even in this extreme case, there is considerable evidence that normal huntingtin is important for neuronal function and that the activity of some of its downstream effectors, such as brain-derived neurotrophic factor, is reduced in Huntington's disease. (nature.com)
Results revealed that TL04 treatment improved cell viability and suppressed reactive oxygen species accumulation, lactose dehydrogenase release and caspase-3 activity, and ameliorated mitochondrial abnormal alteration caused by glutamate. (spandidos-publications.com)
Exposure to glutamate strongly increased the activity of caspase‑8, caspase‑9 and caspase‑3, which were significantly reversed by TL04 pretreatment. (spandidos-publications.com)
However, there is compelling evidence that metacaspases lack caspase activity and that they are not responsible for the caspaselike activities detected during plant and fungal cell death. (rupress.org)

Caspase-3 knock-out mice have increased spine density and altered miniature EPSCs, confirming a physiological involvement of caspase-3 in the regulation of spines in vivo . (jneurosci.org)

Therefore, the delivery of a single miRNA can potentially have a greater, more cumulative effect on HSPs and their downstream effectors than delivering other types of therapeutic molecules such as small interfering RNA (siRNA) molecules or drugs, which can only modulate single HSP-related targets. (cdc.gov)

Within the photostimulated region, local elimination of dendritic spines and dendrite retraction occurred in a caspase-3-dependent manner without inducing cell death. (jneurosci.org)
Such findings suggest that caspase-3 can have a localized effect on the modification of synapses and spines in the absence of cell death. (jneurosci.org)
Using an optogenetic approach (Mito-KillerRed photostimulation), we demonstrate here that caspase-3 can be activated within the neuronal cell body to induce neuronal death or locally within distal dendritic branches to "sculpt" spines and dendrites in the absence of cell death. (jneurosci.org)

Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape. (unibas.ch)

[ 63 ] Accumulation of these memory-effector 'senescent' cells was not associated with their loss of function. (medscape.com)
[ 66 ] In addition, a study demonstrated that CMV seropositivity was associated with a senescent phenotype, that is, a reduction in the frequency of naive T cells and the accumulation of CD45RA-re-expressing late-differentiated effector memory cells. (medscape.com)
Western blot analysis of extracts from Jurkat cells, untreated or etoposide-treated (25 µM), and HeLa cells, untreated or staurosporine-treated (1 µM), using Caspase-7 Antibody. (cellsignal.com)
Noticeably, the mRNA levels of caspase-1 and IL-1β were changed differently in the two cell lines: the level of caspase-1 mRNA was enhanced in IMR-32 cells but suppressed in SK-N-SH cells, and that of IL-1β was suppressed in IMR-32 cells but enhanced in SK-N-SH cells. (researchsquare.com)
This process is further amplified by IL-1β- and IL-23-activated γδ T cells that secrete IL-17 and IL-21 that act in a feedback loop to enhance the Th17 response as part of the effector phase. (springer.com)
Lastly, activated γδ T cells suppress T regulatory (T reg ) responses, promoting the pro-inflammatory profile by effector T cells. (springer.com)

Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of bronchial asthma, with airway clean muscle (ASM) being the effector tissue implicated within the onset of AHR. (aabioetica.org)

Anatomy36

Organisms9

Diseases3

Chemicals and Drugs128

Analytical, Diagnostic and Therapeutic Techniques and Equipment20

Phenomena and Processes58

Disciplines and Occupations1

Information Science3

Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: regulation by the ERK1/2 MAP kinase pathway. (1/11)

Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus. (2/11)

Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop. (3/11)

Reactive-site cleavage residues confer target specificity to baculovirus P49, a dimeric member of the P35 family of caspase inhibitors. (4/11)

Inactivation of effector caspases through nondegradative polyubiquitylation. (5/11)

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring. (6/11)

Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. (7/11)

Gene expression in the brain during reovirus encephalitis. (8/11)

Caspases

Caspase Inhibitors

Apoptosis

Caspase 3

Caspase 6

Caspase 7

Amino Acid Chloromethyl Ketones

Cysteine Proteinase Inhibitors

Caspase 9

Caspases, Effector

Caspase 8

Enzyme Activation

Caspase 2

Caspases, Initiator

Signal Transduction

X-Linked Inhibitor of Apoptosis Protein

Antigens, CD95

Proto-Oncogene Proteins c-bcl-2

Caspase 1

Inhibitor of Apoptosis Proteins

DNA Fragmentation

Cytochrome c Group

Mitochondria

Cysteine Endopeptidases

Jurkat Cells

Apoptotic Protease-Activating Factor 1

Poly(ADP-ribose) Polymerases

Cytochromes c

Cell Death

Cell Line

Mice, Inbred C57BL

Cells, Cultured

Molecular Sequence Data

Amino Acid Sequence

CD8-Positive T-Lymphocytes

bcl-2-Associated X Protein

Caspase 10

BH3 Interacting Domain Death Agonist Protein

Cell Line, Tumor

Apoptosis Regulatory Proteins

Immunologic Memory

Oligopeptides

Tumor Cells, Cultured

Fas Ligand Protein

Cell Survival

Carrier Proteins

Lymphocyte Activation

Enzyme Inhibitors

Granzymes

Flow Cytometry

Mice, Knockout

CD4-Positive T-Lymphocytes

HeLa Cells

bcl-X Protein

Proteins

Cytotoxicity, Immunologic

Protein Binding

Protein Structure, Tertiary

Fas-Associated Death Domain Protein

Apoptosomes

Enzyme Precursors

Blotting, Western

T-Lymphocytes

Apoptosis Inducing Factor

Staurosporine

In Situ Nick-End Labeling

Recombinant Proteins

Models, Biological

Mice, Transgenic

Calpain

Bacterial Proteins

Cell Proliferation

Interferon-gamma

T-Lymphocyte Subsets

Transfection

Mutation

Serpins

Tumor Necrosis Factor-alpha

Annexin A5

HL-60 Cells