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

Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. (1/149)

Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid beta peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families.  (+info)

Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. (2/149)

When accumulation of a malfolded protein in the endoplastic reticulum (ER) is induced by various adverse conditions, such as hypoxia, glucose starvation, and perturbation of calcium homeostasis, cells respond to the stress by increasing transcription of genes encoding ER molecular chaperones, a process known as unfolded protein response. The signaling is initiated by IRE1s, ER stress sensors. Alternatively, excessive stress to the ER results in apoptosis. Caspase-12 is known to be essential for this ER stress-induced apoptosis. In this study, we analyzed the detailed regulatory mechanisms of IRE1s during ER stress. We identified c-Jun N-terminal inhibitory kinase (JIK) as a binding partner of IRE1alpha, and JIK was seen to modulate IRE1alpha-TRAF2 (tumor necrosis factor receptor-associated factor 2) complex formation and the resultant alteration to c-Jun N-terminal kinase signaling from IRE1s in response to ER stress. We also demonstrated that TRAF2 interacts with procaspase-12 and promotes the clustering of procaspase-12 and its activation by cleavage in response to ER stress. These results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s. Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12.  (+info)

Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. (3/149)

The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains destined for secretion or routing into various subcellular compartments. It also regulates cellular responses to stress and intracellular Ca(2+) levels. A variety of toxic insults can result in ER stress that ultimately leads to apoptosis. Apoptosis is initiated by the activation of members of the caspase family and serves as a central mechanism in the cell death process. The present study was carried out to determine the role of caspases in triggering ER stress-induced cell death. Treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin induces the expression of caspase-12 protein and also leads to translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most other members of the caspase family, requires cleavage of the prodomain to activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves the prodomain to generate active caspase-12, resulting in increased cell death. We propose that any cellular insult that causes prolonged ER stress may induce apoptosis through caspase-7-mediated caspase-12 activation. The data underscore the involvement of ER and caspases associated with it in the ER stress-induced apoptotic process.  (+info)

Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation. (4/149)

Endoplasmic reticulum (ER) stress elicits protective responses of chaperone induction and translational suppression and, when unimpeded, leads to caspase-mediated apoptosis. Alzheimer's disease-linked mutations in presenilin-1 (PS-1) reportedly impair ER stress-mediated protective responses and enhance vulnerability to degeneration. We used cleavage site-specific antibodies to characterize the cysteine protease activation responses of primary mouse cortical neurons to ER stress and evaluate the influence of a PS-1 knock-in mutation on these and other stress responses. Two different ER stressors lead to processing of the ER-resident protease procaspase-12, activation of calpain, caspase-3, and caspase-6, and degradation of ER and non-ER protein substrates. Immunocytochemical localization of activated caspase-3 and a cleaved substrate of caspase-6 confirms that caspase activation extends into the cytosol and nucleus. ER stress-induced proteolysis is unchanged in cortical neurons derived from the PS-1 P264L knock-in mouse. Furthermore, the PS-1 genotype does not influence stress-induced increases in chaperones Grp78/BiP and Grp94 or apoptotic neurodegeneration. A similar lack of effect of the PS-1 P264L mutation on the activation of caspases and induction of chaperones is observed in fibroblasts. Finally, the PS-1 knock-in mutation does not alter activation of the protein kinase PKR-like ER kinase (PERK), a trigger for stress-induced translational suppression. These data demonstrate that ER stress in cortical neurons leads to activation of several cysteine proteases within diverse neuronal compartments and indicate that Alzheimer's disease-linked PS-1 mutations do not invariably alter the proteolytic, chaperone induction, translational suppression, and apoptotic responses to ER stress.  (+info)

Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis. (5/149)

The proto-oncogene Bcl-2 is expressed in membranes of mitochondria and endoplasmic reticulum and mediates resistance against a broad range of apoptotic stimuli. Although several mechanisms of Bcl-2 action have been proposed, its role in different cellular organelles remains elusive. Here, we analyzed the function of Bcl-2 targeted specifically to certain subcellular compartments in Jurkat cells. Bcl-2 expression was restricted to the outer mitochondrial membrane by replacing its membrane anchor with the mitochondrial insertion sequence of ActA (Bcl-2/MT) or the ER-specific sequence of cytochrome b5 (Bcl-2/ER). Additionally, cells expressing wild-type Bcl-2 (Bcl-2/WT) or a transmembrane domain-lacking mutant (Bcl-2/DeltaTM) were employed. Apoptosis induced by ionizing radiation or by the death receptors for CD95L or TRAIL was analyzed by determination of the mitochondrial membrane potential (DeltaPsi(m)) and activation of different caspases. Bcl-2/WT and Bcl-2/MT strongly inhibited radiation-induced apoptosis and caspase activation, whereas Bcl-2/DeltaTM had completely lost its anti-apoptotic effect. Interestingly, Bcl-2/ER conferred protection against radiation-induced mitochondrial damage and apoptosis similarly to Bcl-2/MT. The finding that ER-targeted Bcl-2 interfered with mitochondrial DeltaPsi(m) breakdown and caspase-9 activation indicates the presence of a crosstalk between both organelles in radiation-induced apoptosis. By contrast, Bcl-2 in either subcellular position did not influence CD95- or TRAIL-mediated apoptosis.  (+info)

Formation of noncanonical high molecular weight caspase-3 and -6 complexes and activation of caspase-12 during serum starvation induced apoptosis in AKR-2B mouse fibroblasts. (6/149)

Apoptosis is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. In mammals, different complexes like the DISC complex or the apoptosome complexes have been delineated leading to the cleavage and thus activation of the executioner caspases. Although caspase-3 is the main executioner caspase in apoptosis induced by serum starvation in AKR-2B fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial purification of cytosolic extracts by high performance ion exchange chromatography, its activation is apparently caused by a noncanonical pathway: (1) Expression of CrmA, an inhibitor of caspase-8, failed to suppress apoptosis; (2) There was no formation of high molecular weight complexes of Apaf-1 indicative for its activation. Furthermore no cleavage of caspase-9 was observed. But surprisingly, gelfiltration experiments revealed the distribution of caspase-3 and -6 into differently sized high molecular weight complexes during apoptosis. Though the apparent molecular weights of the complexes containing caspase-3 (600 kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently published data, the activity profiles differ strikingly. In AKR-2B cells caspase-3 is mainly recovered as uncomplexed enzyme and in much lower levels in the apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated caspase-3 were devoid of Apaf-1 and cytochrome c. In addition a new 450 kD complex containing activated caspase-6 was found that is clearly separated from the caspase-3 containing complexes. Furthermore, we disclose for the first time the activation of caspase-12 in response to serum starvation. Activated caspase-12 is detectable as non-complexed free enzyme in the cytosol.  (+info)

Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. (7/149)

Accumulation of misfolded proteins and alterations in Ca2+ homeostasis in the endoplasmic reticulum (ER) causes ER stress and leads to cell death. However, the signal-transducing events that connect ER stress to cell death pathways are incompletely understood. To discern the pathway by which ER stress-induced cell death proceeds, we performed studies on Apaf-1(-/-) (null) fibroblasts that are known to be relatively resistant to apoptotic insults that induce the intrinsic apoptotic pathway. While these cells were resistant to cell death initiated by proapoptotic stimuli such as tamoxifen, they were susceptible to apoptosis induced by thapsigargin and brefeldin-A, both of which induce ER stress. This pathway was inhibited by catalytic mutants of caspase-12 and caspase-9 and by a peptide inhibitor of caspase-9 but not by caspase-8 inhibitors. Cleavage of caspases and poly(ADP-ribose) polymerase was observed in cell-free extracts lacking cytochrome c that were isolated from thapsigargin or brefeldin-treated cells. To define the molecular requirements for this Apaf-1 and cytochrome c-independent apoptosis pathway further, we developed a cell-free system of ER stress-induced apoptosis; the addition of microsomes prepared from ER stress-induced cells to a normal cell extract lacking mitochondria or cytochrome c resulted in processing of caspases. Immunodepletion experiments suggested that caspase-12 was one of the microsomal components required to activate downstream caspases. Thus, ER stress-induced programmed cell death defines a novel, mitochondrial and Apaf-1-independent, intrinsic apoptotic pathway.  (+info)

Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. (8/149)

Alterations in Ca(2+) homeostasis and accumulation of unfolded proteins in the endoplasmic reticulum (ER) lead to an ER stress response. Prolonged ER stress may lead to cell death. Glucose-regulated protein (GRP) 78 (Bip) is an ER lumen protein whose expression is induced during ER stress. GRP78 is involved in polypeptide translocation across the ER membrane, and also acts as an apoptotic regulator by protecting the host cell against ER stress-induced cell death, although the mechanism by which GRP78 exerts its cytoprotective effect is not understood. The present study was carried out to determine whether one of the mechanisms of cell death inhibition by GRP78 involves inhibition of caspase activation. Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. GRP78 inhibits cytochrome c-mediated caspase activation in a cell-free system, and expression of GRP78 blocks both caspase activation and caspase-mediated cell death. GRP78 forms a complex with caspase-7 and -12 and prevents release of caspase-12 from the ER. Addition of (d)ATP dissociates this complex and may facilitate movement of caspase-12 into the cytoplasm to set in motion the cytosolic component of the ER stress-induced apoptotic cascade. These results define a novel protective role for GRP78 in preventing ER stress-induced cell death.  (+info)

Necrosis is a type of cell death that occurs when cells are exposed to excessive stress, injury, or inflammation, leading to damage to the cell membrane and the release of cellular contents into the surrounding tissue. This can lead to the formation of gangrene, which is the death of body tissue due to lack of blood supply.

There are several types of necrosis, including:

1. Coagulative necrosis: This type of necrosis occurs when there is a lack of blood supply to the tissues, leading to the formation of a firm, white plaque on the surface of the affected area.
2. Liquefactive necrosis: This type of necrosis occurs when there is an infection or inflammation that causes the death of cells and the formation of pus.
3. Caseous necrosis: This type of necrosis occurs when there is a chronic infection, such as tuberculosis, and the affected tissue becomes soft and cheese-like.
4. Fat necrosis: This type of necrosis occurs when there is trauma to fatty tissue, leading to the formation of firm, yellowish nodules.
5. Necrotizing fasciitis: This is a severe and life-threatening form of necrosis that affects the skin and underlying tissues, often as a result of bacterial infection.

The diagnosis of necrosis is typically made through a combination of physical examination, imaging studies such as X-rays or CT scans, and laboratory tests such as biopsy. Treatment depends on the underlying cause of the necrosis and may include antibiotics, surgical debridement, or amputation in severe cases.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and ... Caspase 12 is a protein that in humans is encoded by the CASP12 gene. The protein belongs to a family of enzymes called ... It is found on chromosome 11 in humans in a locus with other inflammatory caspases.CASP12 orthologs have been identified in ... The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene. The inactive truncated ...
... 2, Caspase 8, Caspase 9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro- ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice These caspases have the ability to induce direct ...
CEDS is caused by homozygous mutations in caspase-8. Caspase-8 is a 51 kb gene with 13 exons encoding for a 496 amino acid ... For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase ... The mutations lead to functional caspase-8 deficiency by destabilizing the caspase-8 protein and inactivating its enzymatic ... Caspase-8 deficiency (CEDS) is a very rare genetic disorder of the immune system. It is caused by mutations in the CASP8 gene ...
CASPASE12, a cysteinyl aspartate proteinase. The loss of this gene is speculated to have reduced the lethality of bacterial ... Of these 12 supported the Homo-Pan clade, 3 the Homo-Gorilla clade, 4 the Pan-Gorilla clade and 16 gave no resolution. ... Retrieved 2010-12-31. Tishkoff, SA.; Reed, FA.; Friedlaender, FR.; Ehret, C.; Ranciaro, A.; Froment, A.; Hirbo, JB.; Awomoyi, ... Usually the molecular clock is calibrated assuming that the orangutan split from the African apes (including humans) 12-16 MYA ...
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 ... Previously activated caspases can cleave caspase-9, causing its dimerization. Caspase-9 has a preferred cleavage sequence of ...
... has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene ... "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct ...
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 ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ...
... is an initiator caspase, as are caspase-8 (EC, caspase-9 (EC and caspase-10 (EC ... Caspase-2 (EC, ICH-1, NEDD-2, caspase-2L, caspase-2S, neural precursor cell expressed developmentally down-regulated ... Caspase-2 at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 3.4.22). ... Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A, Yuan J (August 1997). "Activation of caspase-2 in ...
The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and ... Caspase 7 has been shown to interact with: Caspase 8, Survivin and XIAP. The Proteolysis Map Caspase GRCh38: Ensembl release 89 ... Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved ... Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1998). "Identification and characterization of murine caspase-14, a new member of the caspase family". Cancer Res. 58 (22): ... 2004). "Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin ...
Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important ... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ...
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 ... During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, ...
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 ... For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ...
"AID and Caspase 8 Shape the Germinal Center Response through Apoptosis". The Journal of Immunology. 191 (12): 5840-5847. doi: ... 172 (12): 7432-7441. doi:10.4049/jimmunol.172.12.7432. ISSN 0022-1767. PMID 15187121. Allen, Christopher D. C.; Okada, Takaharu ... A centroblast generally refers to an activated B cell that is enlarged (12-18 micrometer) and is rapidly proliferating in the ... 1025-1063, doi:10.1016/b978-012088451-3.50032-6, ISBN 978-0-12-088451-3 v t e (Articles needing additional references from ...
In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ... In Drosophila melanogaster cells, caspase Dronc is ubiquitylated by Diap-1. Similarly, effector caspases Caspase-3 and Caspase- ... Just as caspase 9 in mammals, caspase Dronc is a protein that has a caspase activation and recruitment domain (CARD). It is the ... Although most human caspases are considered orthologs of caspase Dronc, the one that resembles it the most is Caspase-2. ...
Another more recent example of a disabled gene links the deactivation of the caspase 12 gene (through a nonsense mutation) to ... "Spread of an inactive form of caspase-12 in humans is due to recent positive selection". American Journal of Human Genetics. 78 ... 12 (4): 246-58. doi:10.1038/nrm3089. PMID 21427766. S2CID 5710813. Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, ... 13 (12): 2559-67. doi:10.1101/gr.1455503. PMC 403797. PMID 14656963. Bischof JM, Chiang AP, Scheetz TE, Stone EM, Casavant TL, ...
"Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes ... Alleyne, Richard (12 May 2009). "Men succumb to manflu because women have stronger immune systems, claim scientists". The Daily ... Retrieved 12 September 2011. "NZ Herald - Breaking news, latest news, business, sport and entertainment". Archived from the ...
Involvement of Apoptosis Inducing Factor and Caspase-12". Journal of Medicinal Chemistry. 52 (16): 5176-5187. doi:10.1021/ ... compound induces the death of cancer cells by an original mechanism that involves the apoptosis-inducing factor and caspase 12 ...
"Mylabris phalerata induces apoptosis by caspase activation following cytochrome c release and Bid cleavage". Life Sciences. 73 ... Huh, JE; Kang, KS; Ahn, KS; Kim, DH; Saiki, I; Kim, SH (12 September 2003). " ...
Humans appear to have lost a functional Caspase 12 gene, which in other primates codes for an enzyme that may protect against ... 12 (11): 1663-72. doi:10.1101/gr.338402. PMC 187549. PMID 12421752. (Articles with short description, Short description matches ... 12, 15, 16, 17, and 18. After the completion of the Human genome project, a common chimpanzee genome project was initiated. In ...
May 2012). "Influenza induces endoplasmic reticulum stress, caspase-12-dependent apoptosis, and c-Jun N-terminal kinase- ... at which point human procaspase 4 is believed to cause apoptosis by activating downstream caspases. Although PERK is recognised ... cytochrome c release and caspase 3 activation. Diseases Diseases amenable to UPR inhibition include Creutzfeldt-Jakob disease, ... 12: 20-3. doi:10.1016/0968-0004(87)90011-9. Machamer CE, Doms RW, Bole DG, Helenius A, Rose JK (April 1990). "Heavy chain ...
Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (April 2001). "Activation of caspase-12, an endoplastic ... 8 (12): 982-989. doi:10.1038/nchembio.1094. PMC 3508346. PMID 23086298. Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, ... reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to ... 12 (12): 1812-1824. doi:10.1101/gad.12.12.1812. PMC 316900. PMID 9637683. "Entrez Gene: ERN1 endoplasmic reticulum to nucleus ...
"Effects of galactomyces ferment filtrate on epidermal barrier marker caspase-14 in human skin cells". Journal of the American ... Retrieved 2017-12-03. Lee, Minji; Kim, Hyun-Soo; Cho, Aryeong; Jeon, So Hyeon; Lee, Na Kyeong; Ahn, Kyu Joong; An, In Sook; Lee ... 12 (1): 77-84. Retrieved 2017-12-03. v t e (Articles with short description, Short description matches Wikidata, Articles with ...
2001). "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor- ... v t e (Genes on human chromosome 12, All stub articles, Human chromosome 12 gene stubs). ...
Her group also characterized redundancies between caspase-1 and caspase-8 and between NLRP3 and caspase-8 in autoinflammatory ... Kanneganti's lab showed compensatory roles for NLRP3/caspase-1 and caspase-8 in the regulation of IL-1β production in ... Her lab identified caspase-8 and FADD as expression and activation regulators of both the canonical and non-canonical NLRP3 ... This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in apoptosis. ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... 2005). "Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2". Structure. 12 (12): 2257-63. doi ...
... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn cleaves and activates pro-caspase into ... There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. Accessed 25 March 2007. ...
gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading ... "Tubular cell HIV-1 gp120 expression induces caspase 8 activation and apoptosis". Ren Fail. 31 (4): 303-12. doi:10.1080/ ... "Tubular Cell HIV-1 gp120 Expression Induces Caspase 8 Activation and Apoptosis". Renal Failure. 31 (4): 303-312. doi:10.1080/ ... 14 (12): 1229-1246. doi:10.1093/glycob/cwh106. ISSN 0959-6658. PMID 15175256. Liu Y, Curlin ME, Diem K, Zhao H, Ghosh AK, Zhu H ...
... induced caspase-dependent cleavage of p23. The cleavage could be catalyzed by either caspase-7 or caspase-3 and occurred at ... The Hsp90 inhibitor GA was found to enhance caspase activation, p23 cleavage and apoptosis induced by anthracyclines. Finally ... Gausdal G, Gjertsen BT, Fladmark KE, Demol H, Vandekerckhove J, Døskeland SO (December 2004). "Caspase-dependent, geldanamycin- ... 18 (12): 1989-96. doi:10.1038/sj.leu.2403508. PMID 15483679. Piper PW, Millson SH, Mollapour M, Panaretou B, Siligardi G, Pearl ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 5 (12): 1347-55. PMID 7696183. Lee J, Wang Z, Luoh SM, Wood WI, Scadden DT (January 1994). "Cloning of FRK, a novel human ... 244 (4905): 707-12. Bibcode:1989Sci...244..707S. doi:10.1126/science.2470152. PMID 2470152. Nam S, Kim D, Cheng JQ, Zhang S, ... interactive 3D model of the structure of SRC Vega geneview Src Info with links in the Cell Migration Gateway Archived 2014-12- ...
Wang M, Qanungo S, Crow MT, Watanabe M, Nieminen AL (2005). "Apoptosis repressor with caspase recruitment domain (ARC) is ... NOL3 has been shown to interact with SFRS9 and Caspase 8. GRCh38: Ensembl release 89: ENSG00000140939 - Ensembl, May 2017 ... Ekhterae D, Platoshyn O, Zhang S, Remillard CV, Yuan JX (2003). "Apoptosis repressor with caspase domain inhibits cardiomyocyte ... "Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic ...
Granzymes usually cause apoptosis of the infected cell through initiation of the caspase cascade. However, apoptosis can also ... 14 (12): 1343-1350. doi:10.1038/nm.1884. PMID 19029983. S2CID 2068160. Peña SV, Krensky AM (April 1997). "Granulysin, a new ... 12 (8): e0183610. Bibcode:2017PLoSO..1283610D. doi:10.1371/journal.pone.0183610. PMC 5565109. PMID 28827826. Harris V, Jackson ... 17 (12): 2135. doi:10.3390/ijms17122135. PMC 5187935. PMID 27999358. Krista Conger. Grant to fund research into preventing ...
In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... 12 (10): 1517-22. doi:10.1101/gr.418402. PMC 187523. PMID 12368243. Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, ... 72 (12): 10251-5. doi:10.1128/JVI.72.12.10251-10255.1998. PMC 110608. PMID 9811770. Simon JH, Gaddis NC, Fouchier RA, Malim MH ... 12 (1): 85-98. doi:10.1006/smim.2000.0210. PMID 10723801. Ermolaeva MA, Dakhovnik A, Schumacher B (Jan 2015). "Quality control ...
... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... 81 (12): 2533-2548.e9. doi:10.1016/j.molcel.2021.03.041. PMC 8221569. PMID 33857403. Chen Z, Barbi J, Bu S, Yang HY, Li Z, Gao ... 25 (12): 704-714. doi:10.1089/dna.2006.25.704. PMID 17233114. Jakobsson ME, Moen A, Bousset L, Egge-Jacobsen W, Kernstock S, ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... Archived from the original on 2020-12-03. Retrieved 2019-12-14. van de Craen M, de Jonghe C, van den Brande I, et al. ( ... the sensitivity of PS1 to caspases" (PDF). FEBS Lett. 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/ ... v t e (Genes on human chromosome 12, All stub articles, Human chromosome 12 gene stubs). ...
"Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ... 6 (12): 1245-52. doi:10.1038/ni1271. PMID 16286920. S2CID 24886582. van de Weyer PS, Muehlfeit M, Klose C, Bonventre JV, Walz G ...
If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position ... 13 (1): 102-12. doi:10.1089/cmb.2006.13.102. PMID 16472024. Rønningen T, Shah A, Oldenburg AR, Vekterud K, Delbarre E, Moskaug ... 25 (12): 1825-35. doi:10.1101/gr.193748.115. PMC 4665004. PMID 26359231. Lodish HF, Berk A, Kaiser C, Krieger M, Bretscher A, ...
Hayashi Y, Arakaki R, Ishimaru N (2003). "The role of caspase cascade on the development of primary Sjögren's syndrome". J. Med ... 271 (12): 6636-44. doi:10.1074/jbc.271.12.6636. PMID 8636080. Du A, Sanger JM, Sanger JW (Jun 2008). "Cardiac ... 276 (43): 40104-12. doi:10.1074/jbc.M102454200. PMID 11509555. Chow CW (1999). "Regulation and intracellular localization of ... doi:10.1091/mbc.E05-12-1109. PMC 1415289. PMID 16481394. Bennett PM, Baines AJ, Lecomte MC, Maggs AM, Pinder JC (2004). "Not ...
Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... 20 (13): 4505-12. doi:10.1128/MCB.20.13.4505-4512.2000. PMC 85828. PMID 10848577. Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou ... 274 (15): 10203-12. doi:10.1074/jbc.274.15.10203. PMID 10187805. Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, ... 274 (15): 10203-12. doi:10.1074/jbc.274.15.10203. PMID 10187805. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (1999 ...
... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ... doi:10.1016/b978-0-12-374279-7.02022-1. ISBN 978-0-08-092152-5. Wang GL, Ruan DL, Song WY, Sideris S, Chen L, Pi LY, et al. ( ... 12 of 15 kinases known or predicted to function in PRR signaling fall into the non-RD class. In plants, all PRRs characterized ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 104 (12): 5121-6. Bibcode:2007PNAS..104.5121B. doi:10.1073/pnas.0611030104. PMC 1829273. PMID 17360363. (Genes on human ...
In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator ... 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 ... Differential involvement of caspase-3 and endonuclease G". Journal of Neurovirology. 10 (3): 141-51. doi:10.1080/ ...
Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 36 (12): 2435-44. doi:10.1016/j.biocel.2004.02.013. PMID 15325583. Xie W, Zhang L, Jiao H, Guan L, Zha J, Li X, Wu M, Wang Z, ... 275 (12): 8825-34. doi:10.1074/jbc.275.12.8825. PMID 10722728. Hatakeyama T, Dai P, Harada Y, Hino H, Tsukahara F, Maru Y, ... 13 (12): 960-9. doi:10.1002/elps.11501301199. PMID 1286667. S2CID 41855774. Hattori H, Liu YC, Tohnai I, Ueda M, Kaneda T, ...
It has also been suggested that S1P kinase 2 (SphK2) is a target of caspase 1, and that a cleaved fragment of SphK2 is what is ... In other forms of apoptosis, caspase-1 is not normally induced, meaning the formation of S1P needs to be further studied. S1P ... S1P generation involved caspase-1-dependent release of sphingosine kinase 2 (SphK2) fragments. CX3CL1 release is mediated ... Release is dependent upon caspase activity. Less than 2% of ATP released from the beginning stages of cell death is released ...
2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172-82. doi:10.1038/ ... and it plays a role in the increase of cell survival in a caspase 3 dependent pathway. GRCh38: Ensembl release 89: ... 293 (5532): 1107-12. doi:10.1126/science.1062844. PMID 11498583. S2CID 22700809. Heise CJ, Xu BE, Deaton SL, et al. (2010). " ...
Such substrates have been used to detect caspase activity and cytochrome P450 activity, among others. Luciferase can also be ... All luciferases are classified as oxidoreductases (EC 1.13.12.-), meaning they act on single donors with incorporation of ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... Pidd, Helen (12 November 2020). "UK coronavirus: 33,470 people test positive in a day; NI lockdown extended by a week - as it ... 12 March 2021. Retrieved 13 March 2021. "BBC Radio 4 - Woman's Hour - The Power List 2013". "BBC Radio 4 - Woman's Hour, ... Robson, Steve (12 February 2021). "Manchester University students to hold 'no confidence' vote in Vice Chancellor". Manchester ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... 2013-12-24. Retrieved 2017-03-04. "Search results - 16[CHR] AND "Homo sapiens"[Organism] AND ("has ccds"[Properties] AND alive[ ... 2017-05-12. Retrieved 2017-05-19. "Chromosome 16: Chromosome summary - Homo sapiens". Ensembl Release 88. 2017-03-29. Retrieved ...
... 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: ... 256 (1): 12-8. doi:10.1006/excr.2000.4834. PMID 10739646. Enari, Masato; Sakahira, Hideki; Yokoyama, Hideki; Okawa, Katsuya; ...
2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... 46 (12): 2706-2716. doi:10.1194/jlr.M500313-JLR200. PMID 16170208. Tafesse, F. G.; Ternes, P.; Holthuis, J. C. (2006). "The ... 1758 (12): 2016-2026. doi:10.1016/j.bbamem.2006.08.007. PMID 16996023. Johnson KR, et al. (2003). "Role of human sphingosine-1- ...
"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... The leaves have 12-23 pairs of veins emanating from their midribs. Its petioles are 6-28 by 2.3-5 millimeters and hairless or ... The slightly flattened, elliptical, seeds are 8.5-12 by 6.5-8.5 millimeters. The surface of the seeds are smooth to slightly ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... NACHT, LRR and PYD domains-containing protein 12 is a protein that in humans is encoded by the NLRP12 gene. NALPs are ... "Entrez Gene: NLRP12 NLR family, pyrin domain containing 12". Shami PJ, Kanai N, Wang LY, et al. (2001). "Identification and ...
Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ... "Entrez Gene: Protein phosphatase 3, catalytic subunit, alpha isozyme". Retrieved 2011-12-18. Crabtree GR (March 1999). "Generic ...
2003). "HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear ... 24 (12): 5314-23. doi:10.1128/MCB.24.12.5314-5323.2004. PMC 419898. PMID 15169895. v t e (Articles with short description, ...
Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming death-inducing signaling complex ( ... In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase-independent manner; however, there is still ... In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the other the complex ... HAMLET proceeds by both a multifaceted intrinsic pathway and the caspase cascade, a subsection of the TNF pathway, through ...
During early apoptotic signaling in human endothelial cells, FAK is cleaved by caspase 3 at Asp-772, generating two FAK ... 12 (8): 2290-307. doi:10.1091/mbc.12.8.2290. PMC 58595. PMID 11514617. Turner CE, Brown MC, Perrotta JA, Riedy MC, Nikolopoulos ... ISBN 978-0-12-432565-4. Chan KT, Cortesio CL, Huttenlocher A (2009). "FAK alters invadopodia and focal adhesion composition and ... 272 (12): 7892-8. doi:10.1074/jbc.272.12.7892. PMID 9065456. Girault JA, Labesse G, Mornon JP, Callebaut I (December 1998). " ...
Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway Joo-Sung Yang*1, Mathura P. ... d, The cell lysates were assayed for caspase-9-like activity, and the pcDNA3.1-transfected cell lysate was used as the negative ... c, Colorimetric caspase-3 activity assay using pcWNV-Cp-DJY (Cp-DJY), pcWNV-CpWT (CpWT), or pcWNV-CpΔ3′ (CpΔ3) plasmid- ... e, Inhibition of WNV-Cp-induced apoptosis by a dominant negative (DN) caspase-9 plasmid (DN Casp9) was assayed with equal ...
Inflamassomos; Luz; Camundongos; Animais; Caspase 1; Ritmo Circadiano/fisiologia; Hipocampo; Mamíferos caspase 1; circadian ... In addition to decreased circadian power and reduced locomotor activity, we found cleaved caspase 1 significantly elevated in ... Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mouse Hippocampus. ... Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mous ...
caspase 1. multiple interactions. decreases activity. decreases expression. EXP. ISO. Minocycline inhibits the reaction [HTT ... caspase 3. decreases activity. multiple interactions. decreases expression. ISO. EXP. Minocycline results in decreased activity ... caspase 8. multiple interactions. decreases expression. EXP. Minocycline inhibits the reaction [HTT protein mutant form results ... caspase 9. decreases activity. multiple interactions. decreases expression. ISO. EXP. Minocycline results in decreased activity ...
Examination of these small molecules versus a caspase panel demonstrated an impressive degree of selectivity for caspase 1 ... The small molecular probe ML132 (CID-4462093; NCGC-00183434) is the most potent caspase 1 inhibitor reported to date. It also ... A number of these compounds were potent inhibitors of caspase 1 (IC50s ≤ 1 nM). ... possesses a unique selectivity pattern relative to other reported caspase inhibitors. A number of these compounds were assessed ...
Caspase 12 / drug effects Actions. * Search in PubMed * Search in MeSH * Add to Search ... 2014 Dec;21(12):873-81. doi: 10.1111/jvh.12217. Epub 2013 Dec 18. J Viral Hepat. 2014. PMID: 24351112 ...
MeSH Terms: Animals; Apoptosis/drug effects; Behavior, Animal/drug effects*; Caspase 12/metabolism; Caspase 3/metabolism; Cell ... and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning ... This was accompanied by increased levels of caspase-12 (110%) ...
Regulation of caspase pathways by protein kinase CK2: identification of proteins with overlapping CK2 and caspase consensus ... 6. Caspases and their substrates.. Julien O; Wells JA. Cell Death Differ; 2017 Aug; 24(8):1380-1389. PubMed ID: 28498362. [TBL] ... Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates.. Kumar S; van Raam BJ; Salvesen GS; ... Caspases in developmental cell death.. Shearwin-Whyatt LM; Kumar S. IUBMB Life; 1999 Aug; 48(2):143-50. PubMed ID: 10794589. [ ...
Caspase inhibitor z-LEHD-fmk acts as a selective caspase-9 inhibitor with anti-apoptotic properties. This drug helps decreasing ... Caspase inhibitor Z-DEVD-fmk is a selective caspase-3 inhibitor that also has anti-inflammatory properties. Anti-apoptosis ... caspase-1, and caspase-3. Moreover, minocycline enhances Bcl-2 and thus, reduces apoptosis, also, it decreases p38 mitogen- ... On the other hand, FK506 inhibits caspase-3 and NF-kB, improving functional recovery with the increase of rostral axonal ...
Selenium activated caspases-1 and -12, whereas vitamin E activated caspase-9. Thus, selenium and vitamin E in combination may ... This synergy was accounted for primarily by selenium and vitamin E modifying distinct signaling pathways regulating caspase ... and caspase-3) pathways. The soy isoflavone daidzen has been reported to improve the capacity of tamoxifen to prevent mammary ... Application Research Strategy Length: The R01 application Research Strategy section of the PHS398 may not exceed 12 pages, ...
Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial ... Endo, M.; Mori, M.; Akira, S.; Gotoh, T. C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the ... Cell death proceeds through obvious pathways including the activation of CHOP, JNK and caspase-12. CHOP, an apoptotic ... Cells were treated with different concentrations of ZEA (control, 10, 30 and 50 µM) for 12 h; (C,D) the expression of GRP78 and ...
Caspases [D12.776.476.075.405] * Caspases, Initiator [D12.776.476.075.405.550] * Caspase 1 [D12.776.476.075.405.550.100] ... Caspases [D08.811.277.656.262.500.126] * Caspases, Initiator [D08.811.277.656.262.500.126.550] * Caspase 1 [D08.811.277.656. ... Caspases [D08.811.277.656.300.200.126] * Caspases, Initiator [D08.811.277.656.300.200.126.550] * Caspase 1 [D08.811.277.656. ... A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro- ...
12 113 -12Z/,,/g,,g transform=matrix(.013,0,0,-0.013,32.125,0),,use xlink:href=#g113-49/,,/g,,g transform=matrix(.013,0,0 ... Y. Tian, Y. P. Li, and R. D. Han, "Effects of tetramethylpyrazine on expression of caspase 12 and apoptosis in rats with focal ... High dose of ligustrazine can significantly enhance the expression of Bcl-2 and reduce the expression of p53 [12]. Moreover, ... can attenuate cerebral ischemia reperfusion injury and the protective mechanism may be partly through regulating caspase-12 ...
Loss of UPR signaling results in c-Myc-induced caspase-dependent apoptosis. (A) Perkfl/fl or Perk-/- MEFs infected with control ... This leads to the subsequent activation of caspase-3, -4, and -7 in human cells and of caspase-12 in rodents, which mediate ... We also employed the pan-caspase inhibitory peptide Q-VD-OPH. The addition of Q-VD-OPH prevented c-Myc-induced PARP cleavage ... Published November 12, 2012 - More info Published in Volume 122, Issue 12 on December 3, 2012 J Clin Invest. 2012;122(12):4621- ...
... caspase-2), and the inflammasome (caspase-1 and-11) (16). Executioner or effector caspases, such as caspase-3, -6, and-7 (and ... mainly due to the requirement of inflammatory caspase-1 and/or caspase-11 (murine caspase-11 corresponds to caspases-4 and -5 ... Activated caspase-11 (caspase-4 or caspase-5 in humans), in turn, induces GSDMD cleavage and consequent pyroptosis. ... and the pro-caspase-8, giving rise to the conventional DISC. Next, caspase-8 directly activates the effector caspases or ...
NLRP3, but not the inflammasome adaptor ASC or caspase-1, positively regulated a TH2 program. In TH2 cells, NLRP3 bound the Il4 ... The receptor NLRP3 is involved in the formation of the NLRP3 inflammasome that activates caspase-1 and mediates the release of ... b) mRNA analysis of Il4 and Il13 in mediastinal lymph nodes of WT or Asc−/- or Caspase-1−/- mice naive or 12 days after ... d) Caspase-1 activation was assessed by flow cytometry using FLICA-1 in naive T cells differentiated ex vivo in TH1 or TH2 ...
This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. ... Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. ... Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. ... The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. The FLICA reagent FAM-LETD-FMK enters ... FAM-FLICA® Caspase-8 Assay Kit. from ImmunoChemistry Technologies Product Manual Safety Data Sheet 11 Citations ...
"Alpha helixes surrounded twelve stranded beta sheet structure is unique to caspases" ... 9. Di Lin, Jill Moore, Austin Virtue, Alexander Way - Caspase 3, 1RHK Presentation 4/23/12 Draft due 4/16 ... 2. William Yarr, Ryan Colombo, Joey Nguyen, Jacqueline Pasek-Allen - Hemoglobin 1qxd Presentation 4/27/12 Draft due 4/20 ... 5. Alec Gramann, William Frantz, Felix Alfonso, Paula Preap - Bone Formation & Apoptosis & 1m4u Presentation 4/23/12 Draft due ...
caspase 12 (gene/pseudogene) [Source:.... CCDC93. 54520. CCDC93. coiled-coil domain containing 93 [Sou.... ... The two modules contain 12 novel regulators with no previous implication in Th17 differentiation, which may be essential to ...
Intra- and interdimeric caspase-8 self-cleavage controls strength and timing of CD95-induced apoptosis. ... Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by ... We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an ... Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by ...
2003) Caspase-12 and ER-stress-mediated apoptosis - The story so far APOPTOSIS: FROM SIGNALING PATHWAYS TO THERAPEUTIC TOOLS , ... Hypoxia and ischemia induce nuclear condensation and caspase activation in cardiomyocytes OMahoney, ME,Logue, S,Szegezdi, E, ... Caspase-12 and ER-stress-mediated apoptosis - The story so far Szegezdi, E.,Fitzgerald, U.,Samali, A. (2003) Caspase-12 and ... Samali, A,OMahoney, M,Reeve, J,Logue, S,Szegezdi, E,McMahon, J,Fearnhead, HO (2007) Identification of an inhibitor of caspase ...
图 3 模型对照组和二甲双胍组内质网应激相关蛋白表达电泳图GRP:葡萄糖调节蛋白;PERK:蛋白激酶R样内质网激酶;eIF2α:真核生物起始因子2α;CHOP:C/EBP同源蛋白;caspase:胱天蛋白酶. ... caspase)-12的蛋白表达水平下降(均P,0.05),蛋白激酶R样内质网激酶(PERK)和真核生物起始因子2α(eIF2α)的磷酸化水平下降(均P
Background: Caspase-8. Caspase-8 (Cysteine-aspartic acid protease 8/Casp8; also MCH5 and FLICA) is a 28 kDa member of the ... It is known as the initiating caspase for the apoptotic cascade. Caspase-8 acts on procaspases-3, 4, 6, 7, 9 and 10, in ... Citations for Human Caspase-8 Antibody. R&D Systems personnel manually curate a database that contains references using R&D ... Detection of Human Caspase‑8 by Western Blot. Western blot shows lysates of Jurkat human acute T cell leukemia cell line ...
Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 ...
... combination of low TNF concentration and ethanol through a novel pathway dependent on endoplasmic reticulum-localized caspases- ... 4 and -12, causes the activation of lipogenic transcription factor, SREBP-1 to induce the synthesis of lipogenic enzymes and ...
Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. M. Saleh et al. 0 CASP12 (caspase-12 gene/ ... 2014-12-18 Epidemiology and course of anorexia nervosa in the community. A. Keski-Rahkonen et al. 0 Anorexia and Bulimia 2007 ... Early evidence for bear exploitation during MIS 9 from the site of Schöningen 12 (Germany). I. Verheijen et al. 0 2022 2022-12- ... 2016-03-12 Ecological dominance, social competition, and coalitionary arms races: Why humans evolved extraordinary intelligence ...
Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in ... Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in ... Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in ... Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in ...
Oligomeric IRE1 can also induce the production of directly apoptotic Caspase 12.4 ...
C15 - Standard Human-specific Caspase-8 Antibody. anti-Caspase-8 (human) mAb (C15) ... Phorbol 12-myristate 13-acetate [PMA] - BULK Available. Measure Inflammasome Activation In Vivo using Asc Speck Formation. anti ...
  • 1. Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis. (nih.gov)
  • 7. Hwang-Heuk-San induces apoptosis in HCT116 human colorectal cancer cells through the ROS-mediated activation of caspases and the inactivation of the PI3K/Akt signaling pathway. (nih.gov)
  • 13. Involvement of NLRP3/Caspase-1/GSDMD-Dependent pyroptosis in BPA-Induced apoptosis of human neuroblastoma cells. (nih.gov)
  • It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES . (nih.gov)
  • Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • Peng, Z;Gillissen, B;Richter, A;Sinnberg, T;Schlaak, MS;Eberle, J. Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins . (immunochemistry.com)
  • Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). (ebi.ac.uk)
  • The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis. (ebi.ac.uk)
  • Detects human Caspase-8 precursor in Western blots and a 42 kDa doublet generated during apoptosis. (rndsystems.com)
  • Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in granulosa cells. (ed.ac.uk)
  • Apoptosis was quantified using a luminescent caspase-3/7 assay. (ed.ac.uk)
  • In this study, we used circulating lymphocytes isolated from human blood and found that rotenone (50-250microM, 12-18h) caused apoptosis (phosphatidylserine externalization, caspase 3/7 activation), reactive oxygen species production (superoxide, H2O2), mitochondrial dysfunction (inactivation of complex I, decrease of mitochondria membrane potential, depletion of ATP) and activation of peroxidase activity of mitochondria. (cdc.gov)
  • Smac/DIABLO is required for effector caspase activation during apoptosis in human cells. (mpg.de)
  • Requirement of caspase-mediated cleavage of c-Abl during stress-induced apoptosis. (mpg.de)
  • IMSEAR at SEARO: Role of caspases in apoptosis and disease. (who.int)
  • Khanna N, Singh N. Role of caspases in apoptosis and disease. (who.int)
  • Caspases are synthesized as precursor molecules that require processing at specific aspartate residues to produce the active enzyme which in turn leads to the cleavage of various death substrates that lead to morphological changes typical of apoptosis. (who.int)
  • Since cytotoxic drugs used in chemotherapy of leukemia's and solid tumors cause apoptosis in target cells, elucidating the consequences of proteolytic activity occupies a central role for understanding of the molecular mechanism of apoptosis which can help us to use the caspase inhibitors as targets of therapy. (who.int)
  • 2. Novel Apoptotic Mediators Identified by Conservation of Vertebrate Caspase Targets. (nih.gov)
  • 3. In Vitro Use of Peptide Based Substrates and Inhibitors of Apoptotic Caspases. (nih.gov)
  • 5. Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome. (nih.gov)
  • 14. Cleavage of Armadillo/beta-catenin by the caspase DrICE in Drosophila apoptotic epithelial cells. (nih.gov)
  • 20. Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways. (nih.gov)
  • Caspases are often subcategorized as either pro-apoptotic or pro-inflammatory enzymes. (nih.gov)
  • Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS . (nih.gov)
  • It is known as the initiating caspase for the apoptotic cascade. (rndsystems.com)
  • Oligomeric IRE1 can also induce the production of directly apoptotic Caspase 12. (bellbrooklabs.com)
  • Understanding the mechanism that causes B.al/rapaav to be resistant to activation of the caspase pathway might reveal the basis of differences in the sensitivity to apoptotic stimuli of tumor and normal cells, a key issue in the field of cancer therapeutics. (biomedcentral.com)
  • When the EGL-1 BH3 family protein is produced, it disrupts the cell-protective interaction between the anti-apoptotic CED-9 Bcl-2-family protein and the CED-4 Apaf-1-like protein, releasing CED-4 to activate the pro-apoptotic caspase CED-3 [ 3 - 8 ]. (biomedcentral.com)
  • Recent studies using both molecular and cloning approaches, and in vitro systems have identified a class of highly specific proteases, termed caspases, that appear to have an important role in apoptotic execution. (who.int)
  • an expression level of pro-caspase-9 cleavage products (35-37 kD) was compared to 3′-terminal deletion mutant, pcWNV-Cp∆3′ (Cp∆3′) and pcDNA3.1 by Western blot analysis with anti-human caspase-9 mAb. (cdc.gov)
  • 13. Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. (nih.gov)
  • 17. Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates. (nih.gov)
  • 18. Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain. (nih.gov)
  • 2. Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells. (nih.gov)
  • Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. (ebi.ac.uk)
  • We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. (ebi.ac.uk)
  • In rabbits treated intracisternally with aggregated Aβ(1- 42), clear evidence of endoplasmic reticulum stress was observed by the activation of caspase-12 and cleavage of caspase-3 in the endoplasmic reticulum. (nih.gov)
  • A number of these compounds were potent inhibitors of caspase 1 (IC 50 s ≤ 1 nM). (nih.gov)
  • It also possesses a unique selectivity pattern relative to other reported caspase inhibitors. (nih.gov)
  • Inhibitors of caspase 1 are sought for intervention strategies within ischemic disorders, Huntington's disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, osteoarthritis, inflammatory bowel disease and sepsis. (nih.gov)
  • This review discusses caspases, their inhibitors and regulators. (who.int)
  • 19. Regulation of caspase pathways by protein kinase CK2: identification of proteins with overlapping CK2 and caspase consensus motifs. (nih.gov)
  • 4. Saikosaponin-D induces the pyroptosis of lung cancer by increasing ROS and activating the NF-κB/NLRP3/caspase-1/GSDMD pathway. (nih.gov)
  • 9. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. (nih.gov)
  • 11. Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies. (nih.gov)
  • 12. Suppression of the caspase-1/GSDMD-mediated pyroptotic signaling pathway through dexamethasone alleviates corneal alkali injuries. (nih.gov)
  • 17. Microglial and Neuronal Cell Pyroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway. (nih.gov)
  • We found that B.al/rapaav is resistant to caspase-pathway activation: the caspase-mediated suicide pathway initiates the cell-death process but is insufficient to cause B.al/rapaav death without the subsequent assistance of engulfment. (biomedcentral.com)
  • NCGC-00183434) is the most potent caspase 1 inhibitor reported to date. (nih.gov)
  • This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. (immunochemistry.com)
  • Treatment with lithium, an inhibitor of GSK-3β, inhibited caspase activation but did not prevent mitochondrial DNA damage or tau hyperphosphorylation, suggesting that the translocation of GSK-3β may represent an upstream event that leads to caspase activation but is unrelated to tau hyperphosphorylation or mitochondrial DNA oxidative damage. (nih.gov)
  • Caspase 8 antibody LS-C301799 is an FITC-conjugated rabbit polyclonal antibody to human Caspase 8 (CASP8) (aa217-384). (lsbio.com)
  • the myogenic differentiation was impaired accompanied by the enhanced caspase 12/3 activation, implying enhanced endoplasmic reticulum (ER) stress. (bvsalud.org)
  • c , Colorimetric caspase-3 activity assay using pcWNV-Cp-DJY (Cp-DJY), pcWNV-CpWT (CpWT), or pcWNV-CpΔ3′ (CpΔ3') plasmid-transfected cells. (cdc.gov)
  • Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
  • Bulk Order Inquiry for FAM-FLICA® Caspase-8 Assay Kit ------- (please add any order requirements, including desired quantity, timing, etc. (immunochemistry.com)
  • The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
  • 9. Proteases for cell suicide: functions and regulation of caspases. (nih.gov)
  • Caspases are cysteine proteases with a strict specificity for cleaving peptide sequences C-terminal to aspartic acids residues. (nih.gov)
  • Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. (anthropogeny.org)
  • Caspase 1 is constitutively and inducibly expressed in immune response elements such as T cells, macrophages and neutrophils. (nih.gov)
  • 1. Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells. (nih.gov)
  • 6. Triclabendazole Induces Pyroptosis by Activating Caspase-3 to Cleave GSDME in Breast Cancer Cells. (nih.gov)
  • To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. (ebi.ac.uk)
  • In mutants deficient in the engulfment process, the vast majority of cells still undergo programmed cell death, but the cell corpses persist unengulfed and only slowly degrade [ 10 - 12 ]. (biomedcentral.com)
  • Only a very small number of cells stochastically fail to die in engulfment-defective mutants [ 12 ]. (biomedcentral.com)
  • The 12 h micellar uptake by MGC803 and BGC823 cells was sufficient, and the micelles were able to abundantly accumulate at lesion sites in mice thus achieving good passive EPR targeting. (springer.com)
  • 4. Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues. (nih.gov)
  • 2019 Dec;64(12):3630-3641. (nih.gov)
  • PVDF membrane was probed with 1 µg/mL of Human Caspase-8 Monoclonal Antibody (Catalog # MAB704), followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007 ). (rndsystems.com)
  • Caspase 1, also known as interleukin-converting enzyme or ICE, is responsible for the proteolytic activation of interleukin (IL)-1β and IL-18. (nih.gov)
  • The remaining green fluorescent signal is a direct measure of the active caspase-8 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
  • The receptor NLRP3 is involved in the formation of the NLRP3 inflammasome that activates caspase-1 and mediates the release of interleukin 1β (IL-1β) and IL-18. (nature.com)
  • NLRP3, but not the inflammasome adaptor ASC or caspase-1, positively regulated a T H 2 program. (nature.com)
  • Examination of these small molecules versus a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition. (nih.gov)
  • 15. Effect of phosphorylation and single nucleotide polymorphisms on caspase substrates processing. (nih.gov)
  • 11. A peptide-based target screen implicates the protein kinase CK2 in the global regulation of caspase signaling. (nih.gov)
  • Procaspase 1 is known to associate with several multi-protein complexes capable of responding to numerous external stimuli, suggesting that caspase 1 is a major regulator of the inflammation response. (nih.gov)
  • In addition to decreased circadian power and reduced locomotor activity , we found cleaved caspase 1 significantly elevated in the hippocampus of mice exposed to LL. (bvsalud.org)
  • MYPT1SMKO mice exhibited remarkable white matter injury compared with control mice, as shown by the more prominent loss of myelin at 12 months of age. (bvsalud.org)
  • d , The cell lysates were assayed for caspase-9-like activity, and the pcDNA3.1-transfected cell lysate was used as the negative control. (cdc.gov)
  • Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. (nature.com)
  • 12. Caspase substrates and cellular remodeling. (nih.gov)
  • 7. Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades. (nih.gov)
  • 8. Life-giving caspases: revealing new roles during mouse embryo preimplantation development. (nih.gov)
  • A nitrile-containing propionic acid moiety as an electrophile for covalent attack by the active site cysteine residue of caspase 1 was investigated. (nih.gov)
  • Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. (ebi.ac.uk)
  • Association with another p18/p10 heterodimer generates active caspase-8. (rndsystems.com)
  • 12 months from date of receipt, -20 to -70 °C as supplied. (rndsystems.com)
  • Aliquot and store at -20°C for 12 months. (lsbio.com)
  • This experiment was performed under reducing conditions on the Jess™ Simple Western instrument from ProteinSimple, a BioTechne brand, using the 12-230 kDa separation module. (cellsignal.com)
  • 16. Caspases in developmental cell death. (nih.gov)
  • A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. (nih.gov)
  • Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mouse Hippocampus. (bvsalud.org)
  • High dose of ligustrazine can significantly enhance the expression of Bcl-2 and reduce the expression of p53 [ 12 ]. (hindawi.com)