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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation ... Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.CASP6 orthologs have been identified in numerous mammals for ... Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 ...
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 6 in turn activates HIPK2. Conversely, p53 down regulates HIPK2 by activating the ubiquitin ligase mdm2. An interaction ... The activity of HIPK2 is increased through the action of caspase 6. Caspase 6 cleaves HIPK2 at residue D916 and D977. As a ... MacLachlan TK, El-Deiry WS (July 2002). "Apoptotic threshold is lowered by p53 transactivation of caspase-6". Proceedings of ... p53 binds to the third intron of the caspase 6 gene, and promotes the activation of the gene. ...
Her research focuses especially on caspases, apoptotic proteins involved in the regulation of cell death, and with impacts in ... "Chemist Jeanne A. Hardy to Give Talk at Brookhaven Lab on Caspases, Causative Factor in Neurodegenerative Diseases , 4/24 , BNL ... Hardy, Jeanne A.; Wells, James A. (2009-07-06). "Dissecting an allosteric switch in caspase-7 using chemical and mutational ... Velázquez-Delgado, Elih M.; Hardy, Jeanne A. (2012-10-19). "Zinc-mediated Allosteric Inhibition of Caspase-6". Journal of ...
Pyroptosis (inflammatory caspase-mediated cell death that drives maturation of the cytokines IL-1β and IL-18) and necroptosis ( ... "Discovering the secrets of the enigmatic caspase-6". www.stjude.org. Retrieved 2021-11-16. "Breaking the dogma: Key cell death ... Zheng, Min; Karki, Rajendra; Vogel, Peter; Kanneganti, Thirumala-Devi (April 2020). "Caspase-6 Is a Key Regulator of Innate ...
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. ...
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 ...
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 ... Caspase 8, NLRP1, and XIAP. The Proteolysis Map Caspase Caspase-3 Apoptosome Apaf-1 GRCh38: Ensembl release 89: ENSG00000132906 ...
Initiator Caspases (Caspase 2, Caspase 8, Caspase 9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once ... 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 ...
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 ...
Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by ... Caspase-11 activation by direct binding to LPS represents a novel and unprecedented mechanism for caspase activation. Caspase- ... "Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions". The Journal of Cell ... an inactive precursor to active caspase-11) expression and caspase-11-mediated pyroptosis. Once expressed, caspase-11 is only ...
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 ...
... has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. It ... Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction. Caspase 2 has ... Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
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 ...
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 ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 68 (6): 1157-64. doi:10.1016/j.bcp.2004.05.035. PMID 15313413. Ryu H, Smith K, Camelo SI, Carreras I, Lee J, Iglesias AH, ... 106 (6): 2364-74. doi:10.1111/j.1471-4159.2008.05578.x. PMID 18643871. Nicolia V, Fuso A, Cavallaro RA, Di Luzio A, Scarpa S ( ... 14 (6): 488-92. doi:10.1016/j.cub.2004.03.003. PMID 15043813. S2CID 6465499. Crochemore C, Virgili M, Bonamassa B, Canistro D, ...
2004). "Regulation of caspase-6 and FLIP by the AMPK family member ARK5". Oncogene. 23 (42): 7067-75. doi:10.1038/sj.onc. ... "ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but ...
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 ...
It is also involved in an apoptotic pathway characterized by activation of caspase-6. THOC7 is also part of the same subcomplex ... 6 (1): 19413. doi:10.1038/srep19413. ISSN 2045-2322. Xu, Xiu Qin; Soo, Set Yen; Sun, William; Zweigerdt, Robert (September 2009 ... The gene contains 12 distinct introns, 11 exons, produces 7 different mRNAs, and 6 alternatively spliced variants. The promoter ...
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. ...
... the role of caspase 6 in HD, genetic variation in the human HD gene and the potential of allele-specific gene silencing using ... "Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus". Human Molecular ... "CBC/DNTO: What Happened When You Found A Lost Cause?". Retrieved November 6, 2012. Biography portal Science portal HDBuzz, ... Archived from the original on November 6, 2011. Retrieved November 22, 2011. "Carroll's address to the 2010 Huntington's ...
The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase-7, thereby inhibiting their activation and ... By inhibiting caspase 8, crmA prevents the other caspases from ever being activated. Inhibition of caspase 8 also prevents cell ... Caspase 8 initiates apoptosis by activating "executioner" caspases, numbered 3, 6, and 7. ... By inhibiting caspase 1, also known as interleukin 1β converting enzyme (ICE), crmA prevents cytokines interleukin 1β from ...
... including caspase-1/4/5 in humans and caspase-11 in mice. Pro-apoptotic caspases, including caspase-6/7/8/9, are not required ... caspase-1/4/5 in humans and caspase-11 in mice. These caspases contribute to the maturation and activation of several ... of gram-negative bacteria directly onto caspase-4/5 in humans and caspase-11 in murines. Binding of LPS onto these caspases ... Caspase-3, an executioner caspase in apoptosis, can cleave gasdermin E (GSDME) to produce a N-terminal fragment and a C- ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... 1] Apoptosis, Trail & Caspase 8 - The Proteolysis Map-animation PDB: 1D2Q​ TRAIL+Protein at the US National Library of Medicine ... Feb 2016 Song JJ, Lee YJ (May 2008). "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation ... 3 (6): 673-82. doi:10.1016/1074-7613(95)90057-8. PMID 8777713. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi ...
2007). "Cells with defective p53-p21-pRb pathway are susceptible to apoptosis induced by p84N5 via caspase-6". Cancer Res. 67 ( ...
Caspase activity that is triggered by the NLRP1 inflammasome activates caspase-6, which destroys the axons of neurons. Plants ... NOD-like receptors, in general, activate caspase-1 and assist in the maturation of the proinflammatory cytokines IL-1β and IL- ... However, not every NLRP forms an inflammasome and activates caspase-1; these NLRPs are referred to as non-canonical NLRPs. As ... including K+ efflux and caspase 1 activation. NLRPs are also known to be associated with a number of diseases. Research ...
"Entrez Gene: CARD10 caspase recruitment domain family, member 10". Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S ... Caspase recruitment domain-containing protein 10 is a protein in the CARD-CC protein family that in humans is encoded by the ... The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates ... "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and ...
2010). Cleavage at the 586 Amino Acid Caspase-6 Site in Mutant huntingtin Influences Caspase-6 Activation In Vivo. The Journal ... 6. 10.1016/j.jalz.2010.05.923. Kudo, Lili & VI, Nancy & Lau, Kimbley & Parfenova, Liubov & Hui, Maria & Gray, Michelle & Yang, ...
Galande S, Dickinson LA, Mian IS, Sikorska M, Kohwi-Shigematsu T (August 2001). "SATB1 cleavage by caspase 6 disrupts PDZ ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (October ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T (August 1992). "A ... 280 (6): 5004-12. doi:10.1074/jbc.M411718200. PMID 15561718. Wen J, Huang S, Rogers H, Dickinson LA, Kohwi-Shigematsu T, ...
S30-S38 Graham, RK; Deng, Y; Slow, EJ; et al.Cleavage at the caspase-6 site is required for neuronal dysfunction and ... Surprisingly, both necrotic and apoptotic processes utilize a similar intracellular signaling cascade which uses caspase ... and Morphine-6-Glucuronide-induced Respiratory Depression in Healthy Volunteers: A Mechanism-based Pharmacokinetic- ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 4 (6): 799-822. doi:10.4155/fmc.12.29. PMID 22530642. Breccia M, Salaroli A, Molica M, Alimena G (2013). "Systematic review of ... 6: 99-106. doi:10.2147/OTT.S19901. PMC 3594007. PMID 23493838. Mshaik R, Simonet J, Georgievski A, Jamal L, Bechoua S, ... 6: 257-65. doi:10.2147/OTT.S35360. PMC 3615898. PMID 23569389. Amsberg GK, Koschmieder S (2013). "Profile of bosutinib and its ...
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 ... 157 (6): 1309-1323. doi:10.1016/j.cell.2014.03.062. PMC 4090916. PMID 24906149. da Silva AP, Unks D, Lyu SC, Ma J, Zbozien- ... 170 (6): 3154-3161. doi:10.4049/jimmunol.170.6.3154. PMID 12626573. Ogawa K, Takamori Y, Suzuki K, Nagasawa M, Takano S, ... 158 (6): 2680-2688. PMID 9058801. Hanson DA, Kaspar AA, Poulain FR, Krensky AM (May 1999). "Biosynthesis of granulysin, a novel ...
In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... 33 (4): 415-6. doi:10.1016/j.molcel.2009.02.007. PMID 19250902. Isono E, Nishihara K, Saeki Y, Yashiroda H, Kamata N, Ge L, ... 44 (6): 907-17. doi:10.1016/j.molcel.2011.11.020. PMC 3251515. PMID 22195964. Pathare GR, Nagy I, Śledź P, Anderson DJ, Zhou HJ ... 24 (6): 352-9. doi:10.1016/j.tcb.2013.12.003. PMC 4037451. PMID 24457024. Goldberg, AL; Stein, R; Adams, J (August 1995). "New ...
... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... 7 (6): 1252-1269. PMC 5489776. PMID 28670489. Garg M, Kanojia D, Seth A, Kumar R, Gupta A, Surolia A, Suri A (January 2010). " ... The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous ... 86 (6): 1968-1972. Bibcode:1989PNAS...86.1968S. doi:10.1073/pnas.86.6.1968. PMC 286826. PMID 2538825. Rosenzweig R, Nillegoda ...
"Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone". ... 52 (6): 252-8. doi:10.1016/S0753-3322(98)80010-3. PMID 9755824. Li X, Darzynkiewicz Z (1995). "Labeling DNA strand breaks with ... 55 (6): 615-621. doi:10.1262/jrd.20250. PMID 19734695. Gorczyca W, Bruno S, Darzynkiewicz RJ, Gong J, Darzynkiewicz Z (1992). " ... 1 (6): 639-648. doi:10.3892/ijo.1.6.639. PMID 21584593. Gavrieli Y, Sherman Y, Ben-Sasson SA (1992). "Identification of ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... 378 (6): 565-71. doi:10.1515/bchm.1997.378.6.565. PMID 9224939. Zhang WJ, Wu JY (Feb 1998). "Sip1, a novel RS domain-containing ... the sensitivity of PS1 to caspases" (PDF). FEBS Lett. 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/ ...
"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 ... 351 (2): 571-6. doi:10.1016/j.bbrc.2006.10.079. PMID 17069754. Overview of all the structural information available in the PDB ... 13 (6): 2503-9. doi:10.7314/apjcp.2012.13.6.2503. PMID 22938412. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, ...
If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position ... All of these genes are located in histone cluster 1 on chromosome 6 and cluster 2 and cluster 3 on chromosome 1. In each gene ...
Hayashi Y, Arakaki R, Ishimaru N (2003). "The role of caspase cascade on the development of primary Sjögren's syndrome". J. Med ... 48 (6): 1050-9. doi:10.1016/j.yjmcc.2010.01.001. PMC 3537504. PMID 20114050. Cianci CD, Zhang Z, Pradhan D, Morrow JS (Nov 1999 ... 53 (6): e106-10. doi:10.1111/j.1528-1167.2012.03437.x. PMID 22429196. S2CID 20216273. Jain P, Spaeder MC, Donofrio MT, Sinha P ... 270 (32): 18990-6. doi:10.1074/jbc.270.32.18990. PMID 7642559. Gregorio CC, Repasky EA, Fowler VM, Black JD (1994). "Dynamic ...
Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... 7 (6): 821-30. doi:10.1016/S1074-7613(00)80400-8. PMID 9430227. Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, Vincenz C, ... 5 (6): 1051-7. doi:10.1016/s1097-2765(00)80270-1. PMID 10911999. Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, ... 5 (6): 1051-7. doi:10.1016/S1097-2765(00)80270-1. PMID 10911999. TRADD+Protein at the US National Library of Medicine Medical ...
... 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. ... 15 (6): 779-791. doi:10.1016/j.chom.2014.05.004. PMC 4085166. PMID 24882704. Kim YG, Park JH, Shaw MH, Franchi L, Inohara N, ... 6 (1): 9-20. doi:10.1038/nri1747. PMID 16493424. S2CID 33505741. Burberry A, Zeng MY, Ding L, Wicks I, Inohara N, Morrison SJ, ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 11 (6): 1053-70. doi:10.1101/gr.154901. PMC 311098. PMID 11381032. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, ... 104 (12): 5121-6. Bibcode:2007PNAS..104.5121B. doi:10.1073/pnas.0611030104. PMC 1829273. PMID 17360363. (Genes on human ... and 6 (CerS6), thereby blocking CerS2/6 complex formation and activity. Thus, inhibiting BCL2L13 during cancer treatments may ...
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- ... 62 (6): 670-684. doi:10.1007/s00018-004-4464-6. PMC 2773841. PMID 15770419. Wang X, Wang Q, Lin H, Li S, Sun L, Yang Y (Feb ... 274 (2): 781-6. doi:10.1074/jbc.274.2.781. PMID 9873016. Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, ... 14 (6): 450-9. doi:10.1038/sj.cr.7290247. PMID 15625011. S2CID 21654486. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE ...
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: ... 20 (6): 1314-22. doi:10.1681/ASN.2008050542. PMC 2689907. PMID 19470686. Auffray C, Behar G, Bois F, et al. (1995). "[IMAGE: ... doi:10.1007/s00018-010-0261-6. PMID 20094755. S2CID 32790065. Talmud PJ, Drenos F, Shah S, et al. (2009). "Gene-centric ...
Such substrates have been used to detect caspase activity and cytochrome P450 activity, among others. Luciferase can also be ... 5 (6): 798-809. doi:10.1016/0959-440x(95)80014-x. PMID 8749369. Schultz LW, Liu L, Cegielski M, Hastings JW (Feb 2005). " ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... 6 (4): 1043-1048. doi:10.1242/dmm.011601. PMC 3701223. PMID 23519030. Rothwell, Nancy (2002). Who wants to be a scientist?: ... 6 (3): 187-194. doi:10.1111/j.1747-4949.2010.00561.x. PMID 21557802. S2CID 25940748. "The Life Scientific; Nancy Rothwell". ... 6 November 2020. Retrieved 13 November 2020. Robson, Steve (12 November 2020). "Students 'occupy' University of Manchester ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... encoding protein ADP-ribosylation factor-like protein 6-interacting protein 1 ARMC5 BMIQ5: Body mass index quantitative trait ... encoding protein Transport and Golgi organization protein 6 homolog TAO2: encoding Serine/threonine-protein kinase TAO2 TBC1D24 ... encoding enzyme M-phase phosphoprotein 6 MT1G: encoding protein Metallothionein-1G MT1X: encoding protein Metallothionein 1X ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... 2002). "Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1". ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
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 ... J. 21 (6): 295-304. doi:10.1023/B:GLYC.0000046272.38480.ef. PMID 15514478. S2CID 19898617. Xu, R.; et al. (2006). "Golgi ... 134 (6): 921-31. doi:10.1016/j.cell.2008.09.002. PMC 2632951. PMID 18805086. (Articles with short description, Short ...
"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... Its flowers have 6 petals in two rows of three. The oval to narrowly elliptical outer petals are 10-28 by 4.5-11.5 millimeters ... Its petioles are 6-28 by 2.3-5 millimeters and hairless or sparsely hairy. Its solitary flowers grow on 5-11.5 by 1.2-3 ... 88: 1-6. doi:10.1016/j.fitote.2013.03.028. ISSN 0367-326X. PMID 23570840. (CS1 Dutch-language sources (nl), CS1 Latin-language ...
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 ... 179 (9): 6291-6. doi:10.4049/jimmunol.179.9.6291. PMID 17947705. Chen L, Wilson JE, Koenigsknecht MJ, et al. (2017). "NLRP12 ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
2003). "HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear ... 31 (6): 446-54. doi:10.1016/S0301-472X(03)00083-3. PMID 12829019. Soares MB, Bonaldo MF, Jelene P, et al. (1994). "Construction ... 446 (1): 6-8. doi:10.1016/S0014-5793(99)00173-8. PMID 10100603. Soldani C, Scovassi AI (2003). "Poly(ADP-ribose) polymerase-1 ... 62 (3): 533-6. doi:10.1006/geno.1999.6024. PMID 10644454. "Entrez Gene: PARP4 poly (ADP-ribose) polymerase family, member 4". ...
... an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti- ... May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute ... The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects. It was developed for the ... November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal ...
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 ...
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, ... 287 (5453): 664-6. Bibcode:2000Sci...287..664U. doi:10.1126/science.287.5453.664. PMID 10650002. Ozcan U, Cao Q, Yilmaz E, Lee ...
Caspases/química Caspases/genética Primers do DNA DNA Complementar Ativação Enzimática Genoma Dados de Sequência Molecular ... Caspy, a zebrafish caspase, activated by ASC oligomerization is required for pharyngeal arch development.. Masumoto, Junya; ... These studies suggest that zAsc mediates the activation of Caspy, a caspase that plays an important role in the morphogenesis ... Caspases/metabolismo Proteínas do Citoesqueleto/metabolismo Faringe/embriologia Proteínas de Peixe-Zebra/metabolismo Peixe- ...
Antibody Details for Caspase-6. WBI Title. Validation Status. Band Result. Date. Dilution. ...
Caspase Independent Cell Death in Malignant Breast Cancer Cells MDA MB-231 by Chalcone Derivatives Cite this Research ... Ginger extract activates caspase-independent paraptosis in cancer cells via ER stress, mitochondrial dysfunction Cite this ... Role of AIF in Plumbagin induced Paraptosis-A caspase independent cell death in MDA-MB-231 cancer cells Cite this Research ... Oxyresveratrol Drives Caspase-independent Apoptosis-like Cell Death in MDA-MB-231 Breast Cancer Cells through the Induction of ...
Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway ... Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver ... and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. ... Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later ...
Caspase 9 (1) Cathepsin B (1) Cathepsin L (1) Complement factor (1) ...
Caspase expression in oral squamous cell carcinoma.. Coutinho-Camillo CM; Lourenço SV; Nishimoto IN; Kowalski LP; Soares FA. ...
HSP70 is released by caspase-dependent lysosomal exocytosis from LAMP3-overexpressing epithelial cells. (A-H) HSG cells were ... 6 , Cuong Q Nguyen 7 , Masayuki Noguchi 8 , Tatsuya Atsumi 9 , Blake M Warner 1 2 , John A Chiorini 1 ... 6 , Cuong Q Nguyen 7 , Masayuki Noguchi 8 , Tatsuya Atsumi 9 , Blake M Warner 1 2 , John A Chiorini 1 ... Scale bars: 50 μm and 10 μm (insets). (B) Mean (± SD) number of BMP6+ dots per mm2 (n = 7 patients with SS and n = 6 non-SS ...
An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science 367:doi:10.1126/science.aay0542 PMID: ... ER stress drives lipogenesis and steatohepatitis via caspase-2 activation of S1P. Cell 175(1):133-145. doi:10.1016/j.cell. ... NCOA5, IL-6, type 2 diabetes, and HCC: the deadly quartet. Cell Metab 19(1):6-7. doi:10.1016/j.cmet.2013.12.010 PMID:24411937 ... Trends Immunol 25(6):280-288. PMID:15145317 *Galijatovic A, Beaton D, Nguyen N, Chen S, Bonzo JA, Johnson RS, Maeda S, Karin M ...
Lamin A/C is cleaved by caspase-6 and serves as a marker for caspase-6 activation. The cleavage of lamins results in nuclear ... produced by caspase cleavage during apoptosis. Cleaved Lamin A (Small Subunit) (30H5) Mouse mAb detects endogenous levels of ... and ASC/TMS1 has been found to be a critical component of inflammatory signaling where it associates with and activates caspase ... 6). Rab11FIP1 has been shown to play a role in endocytic sorting and trafficking of EGFR and integrin subunits (6). Integrins ...
... pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. We now report that IL-1β and TNFα ... pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. We now report that IL-1β and TNFα ... sensitized to FasL-induced caspase-3 activation and cell death. However, when TNFα action was blocked by neutralizing ... sensitized to FasL-induced caspase-3 activation and cell death. However, when TNFα action was blocked by neutralizing ...
It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... Caspases [D12.776.476.075.405] * Caspases, Effector [D12.776.476.075.405.350] * Caspase 3 [D12.776.476.075.405.350.300] ... Caspases [D08.811.277.656.262.500.126] * Caspases, Effector [D08.811.277.656.262.500.126.350] * Caspase 3 [D08.811.277.656. ...
Caspase-3 (Pharmingen, San Diego, CA), caspase-8 (FADD-like interleukin-1 beta-converting enzyme) and caspase-9-like Mch6 (MBL ... The DN caspase-9 specifically blocked the cleavage of pro-caspase-9 in pcWNV-Cp-DJY and pcWNV-CpWT cotransfected cell lysates ... The cell lysates (100 μg/100 μl protein) were incubated with specific substrate Ac-DEVD-AMC for caspase-3, IETD-pNA for caspase ... Furthermore, to confirm that this apoptosis-induction pathway is through caspase-9, a domant negative (DN) caspase-9 construct ...
Ordering the cytochrome C-initiated caspase cascade: Hierarchial activation of caspases-2, -3, -6, -7, -8 and -10 in a caspase- ... caspases, bcl-2 family members, caspase inhibitors, and DNA repair enzymes, and/or their influence on any of the above ... BAX translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, BCL-2, and caspases. J. Neurosci. ... induces the entire caspase cascade involved in apoptosis (Slee et al., 1999). Furthermore, critical mitochondrial proteins ...
Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the ... N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via ... The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. ... ab126732 has been referenced in 6 publications.. *Wang T et al. Regulation of Th17/Treg Balance by 27-Hydroxycholesterol and ...
This effect is associated with an increase of caspase-3 and a decrease of interleukin-6 production. Therefore, the effects of ...
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 ...
Targets Caspase-9, ERK 1/2 and the Wnt3a/β-Catenin Pathway in Medulloblastoma Cells and Medulloblastoma Cell Spheroids. ... blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6.. Zhao H; Zhang X; ... Int J Pharm; 2009 May; 373(1-2):100-6. PubMed ID: 19429294. [TBL] ... Int J Cancer; 2002 Aug; 100(5):520-6. PubMed ID: 12124800. [TBL] ...
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 ...
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 ...
Identification of Protease Inhibitor- Caspase-6. Editorial: J Appl Bioinforma Comput Biol 2020, 9:4. DOI: 10.37532/2329- ... Research Article: J Appl Bioinforma Comput Biol 2017, 6:2. DOI: 10.4172/2329-9533.1000133. Vaibhav Sabale and Arun G Ingale. * ... Short Communication: J Appl Bioinforma Comput Biol 2020, 9:6. DOI: 10.37532/2329-9533.2020.9(6).188. Navya Sree Nuthalapati1* * ... Commentary: J Appl Bioinforma Comput Biol 2020, 9:6. DOI: 10.37532/2329-9533.2020.9(6).189. Navya Sree Nuthalapati* *Abstract ...
... caspase 9 activates downstream effector caspases (i.e., caspase 6), and upregulates the levels of cleaved-caspase 6 (32). In ... B-E) Protein expression levels of cleaved-caspase 9, cleaved-caspase 6, p-Akt, Akt, p-MDM2, MDM2, p53 and Bax were examined via ... F) Western blotting was used to analyze the protein expression levels of cleaved-caspase 9, cleaved-caspase 6 and Bax. β-actin ... G) Relative protein expression levels of Bax, cleaved-caspase 9, cleaved-caspase 6 were semi-quantified. (H and I) The protein ...
Cleaved caspase-3 levels in HM cells treated with 5 μg/cm2 crocidolite for 24 h. (G) Foci formation after 4 wk of culture in HM ... Cleaved caspase-3 levels and transmembrane TNF-α levels. (I) TNF-α levels in the culture media measured by ELISA; results are ... 6 , Joseph J Grzymski 7 , Muzaffer Metintas 3 , Muhittin Akarsu 8 , Betsy Morrow 9 , Raffit Hassan 9 , Haining Yang 10 , ... 6 , Joseph J Grzymski 7 , Muzaffer Metintas 3 , Muhittin Akarsu 8 , Betsy Morrow 9 , Raffit Hassan 9 , Haining Yang 10 , ...
... lung microenvironment suppresses carbon nanotube-induced inflammasome activation via STAT6-dependent inhibition of caspase-1. ... 10(6): e0128888.]. *Taylor AJ, McClure CD, Shipkowski KA, Thompson EA, Hussain S, Garantziotis S, Parsons GN, Bonner JC. (2014 ... 10(6): e0128888. [Abstract Shipkowski KA, Taylor AJ, Thompson EA, Glista-Baker EE, Sayers BC, Messenger ZJ, Bauer RN, Jaspers I ... lung microenvironment suppresses carbon nanotube-induced inflammasome activation via STAT6-dependent inhibition of caspase-1. ...
It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... Caspase 6 - Preferred Concept UI. M0275238. Scope note. A short pro-domain caspase that plays an effector role in APOPTOSIS. ... Caspase-6. Tree number(s):. D08.811.277.656.262.500.126.350.600. D08.811.277.656.300.200.126.350.600. D12.776.476.075.405.350. ...
It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to ... Caspases [D12.776.476.075.405] * Caspases, Effector [D12.776.476.075.405.350] * Caspase 3 [D12.776.476.075.405.350.300] ... Caspases [D08.811.277.656.262.500.126] * Caspases, Effector [D08.811.277.656.262.500.126.350] * Caspase 3 [D08.811.277.656. ...
Amplite™ Fluorimetric Caspase 3/7 Assay Kit *Green Fluorescence*. 13503 AAT Bioquest 500 Tests. ... 10-6 cm2 s-1) had been obtained within the agarose/PVA mannequin. ... Canadian Pesticide Kit Containing All 6 Mixes. CAN-CAN-KIT ...
2 protein levels and proform caspase-3 and caspase-7 protein expression levels and increase in proform of caspase-8 and caspase ... It was also observed the increased activity of caspase-3, caspase-8, and caspase-9, reduced levels of PARP and Bcl-2, and ... Cleavage of caspase-3, caspase-8, caspase-9, PARP and upregulation of Fas, p53, p21, and Bax/Bcl-2 ratio levels were also ... reported that application of 10 μM aloe emodin and 12.8 J/cm2 illuminating energy enhanced the levels of caspase-3 and caspase- ...
... by monitoring cleavage of cellular caspase-1 substrates, processing of caspase-1 itself, or by quantifying cell death. Caspase ... Inflammatory Caspase-1 has a significant impact on AD-like pathophysiology and Caspase-1 inhibitor, VX-765, reverses cognitive ... Pre-symptomatic caspase-1 inhibitor delays cognitive decline in a mouse model of Alzheimer disease and aging BIBLIOGRAPHIC ... Pharmacodynamics: The caspase-1 protease is a core component of multiprotein inflammasome complexes, which play a critical role ...
  • 7. Identification of the novel substrates for caspase-6 in apoptosis using proteomic approaches. (nih.gov)
  • 10. A Review on Caspases: Key Regulators of Biological Activities and Apoptosis. (nih.gov)
  • 15. Initiator and executioner caspases in salivary gland apoptosis of Rhipicephalus haemaphysaloides. (nih.gov)
  • 16. Changes in nuclear morphology during apoptosis correlate with vimentin cleavage by different caspases located either upstream or downstream of Bcl-2 action. (nih.gov)
  • 17. In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis. (nih.gov)
  • The results of the current study revealed a number of non-peptide-based caspase inhibitors that may be useful in assessing the role of inhibiting the executioner caspases in minimizing tissue damage in disease conditions characterized by unregulated apoptosis. (nih.gov)
  • Brief exposure to the pan-caspase apoptosis inhibitor Z-VAD-FMK restored attachment ability and promoted a differentiated morphology, as well as formation of 3D spheroids. (springer.com)
  • 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)
  • A short pro-domain caspase that plays an effector role in APOPTOSIS . (nih.gov)
  • Further, canagliflozin prevents ISO-induced apoptosis of kidney cells by inhibiting Bax protein upregulation and caspase-3 activation. (nature.com)
  • Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
  • We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
  • 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)
  • Subsequently, flow cytometry and western blotting indicated that involucrasin A induced apoptosis and upregulated the expression levels of apoptosis‑related proteins, such as cleaved‑caspase 6 and cleaved‑caspase 9, in a dose‑dependent manner. (spandidos-publications.com)
  • Caspasa de prodominio corto que desempeña una función efectora en la APOPTOSIS. (bvsalud.org)
  • 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)
  • Inflammatory Caspase-1 has a significant impact on AD-like pathophysiology and Caspase-1 inhibitor, VX-765, reverses cognitive deficits in AD mouse models. (nih.gov)
  • The Group III Caspase Inhibitor I controls the biological activity of Group III caspases (caspase-6, -8, -9, and -10). (emdmillipore.com)
  • Only caspase 9 inhibitor totally abrogated γTriDAP cytotoxicity. (biomedcentral.com)
  • 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)
  • 9. Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes. (nih.gov)
  • Isatin sulfonamide analogs containing a Michael addition acceptor: a new class of caspase 3/7 inhibitors. (nih.gov)
  • Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6. (nih.gov)
  • Caspase 8 antibody LS-C301799 is an FITC-conjugated rabbit polyclonal antibody to human Caspase 8 (CASP8) (aa217-384). (lsbio.com)
  • We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). (hopkinsmedicine.org)
  • Western blot analysis was performed to investigate the effects of royal jelly on the protein expression levels of Bax, caspase-3 , caspase-6 , Bcl-2, NF-κB, COX-2, and Erk. (bvsalud.org)
  • Additionally, the protein expression of caspase-3 , caspase-6 , Bax, and Erk were decreased in fluoride -treated groups and they were significantly increased by RJ treatment compared to the un -treated rats . (bvsalud.org)
  • 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)
  • and protein carbonyl, IL-1B, and caspase-1 determination. (cdc.gov)
  • For a caspase-9-specific test, 5 μg of pcWNV-Cp-DJY or pcWNV-CpWT was cotransfected with a dominant negative caspase-9 (DN caspase-9) construct, and cleavage of procaspase-9 protein was determined by Western blot analysis with antihuman caspase-9 antibody (MBL, Nagoya, Japan). (cdc.gov)
  • 18. Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. (nih.gov)
  • It is known as the initiating caspase for the apoptotic cascade. (rndsystems.com)
  • 1. Exogenous Introduction of Initiator and Executioner Caspases Results in Different Apoptotic Outcomes. (nih.gov)
  • Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, were identified. (nih.gov)
  • The localization pattern of capsid expression was analyzed by immunofluorescent assay in HeLa, 293-T, RD, or SH-SY5Y cells by using anti-His tag antibody as described ( 6 ). (cdc.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)
  • 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)
  • 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)
  • Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. (cdc.gov)
  • Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. (cdc.gov)
  • 3. Death and survival from executioner caspase activation. (nih.gov)
  • The treatment of hepatocytes with the BMDM supernatant, which contains both IL-1β and TNFα, sensitized to FasL-induced caspase-3 activation and cell death. (frontiersin.org)
  • 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)
  • 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)
  • The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
  • Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. (cdc.gov)
  • Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. (cdc.gov)
  • Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. (cdc.gov)
  • Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. (cdc.gov)
  • Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. (cdc.gov)
  • Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. (cdc.gov)
  • Caspases are cysteine proteases with a strict specificity for cleaving peptide sequences C-terminal to aspartic acids residues. (nih.gov)
  • 12. Suppression of the caspase-1/GSDMD-mediated pyroptotic signaling pathway through dexamethasone alleviates corneal alkali injuries. (nih.gov)
  • These compounds were also observed to have a low potency for inhibiting the initiator caspases, caspase-1 and caspase-8, and caspase-6. (nih.gov)
  • Currently, 12 caspase isozymes have been identified in humans, with numerous reported activities. (nih.gov)
  • Infection with multiple herpes viruses, for instance, is an inextricable part of the human condition , to which more than 90% of humans are subject (6). (oneradionetwork.com)
  • A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. (nih.gov)
  • 9. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. (nih.gov)
  • Also inhibits caspase-1 and caspase-3. (emdmillipore.com)
  • These results suggest that Caspase-1-mediated inflammation occurs early in the disease and raise hope that VX-765, a previously Food and Drug Administration-approved drug for human CNS clinical trials, may be a useful drug to prevent the onset of cognitive deficits and brain inflammation in AD. (nih.gov)
  • Royal jelly protects brain tissue against fluoride-induced damage by activating Bcl-2/NF-κB/caspase-3/caspase-6/Bax and Erk signaling pathways in rats. (bvsalud.org)
  • This study is aimed at determining whether royal jelly (RJ) which has a powerful antioxidant property prevents fluoride -induced brain tissue damage and exploring whether Bcl-2/NF-κB/ and caspase-3 / caspase-6 /Bax/ Erk pathways play a critical role in the neuroprotective effect of RJ. (bvsalud.org)
  • Whereas TNFα preincubation leads to elevated levels of caspase-3 activity and cell death, pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. (frontiersin.org)
  • 1. Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells. (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)
  • 6. Triclabendazole Induces Pyroptosis by Activating Caspase-3 to Cleave GSDME in Breast Cancer Cells. (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)
  • DN caspase-9 (provided courtesy of Emad S. Alnmeri, Thomas Jefferson University, Philadelphia, PA) has been reported to inhibit the caspase cascade ( 5 ). (cdc.gov)
  • Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. (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)
  • 2021 Aug 31;6(4):e0030621. (nih.gov)
  • 2021 Jun 29;6(3):e0033621. (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)
  • Examination of these small molecules versus a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition. (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)
  • Caspases are often subcategorized as either pro-apoptotic or pro-inflammatory enzymes. (nih.gov)
  • 14. Role and Association of Inflammatory and Apoptotic Caspases in Renal Tubulointerstitial Fibrosis. (nih.gov)
  • Natural products are a key source of new antitumorigenic agents, as 80-83% of approved anticancer drugs are natural compounds or their derivatives ( 6 ). (spandidos-publications.com)
  • 11. The enigmatic roles of caspases in tumor development. (nih.gov)
  • This effect is associated with an increase of caspase-3 and a decrease of interleukin-6 production. (minervamedica.it)
  • Caspase 1 is constitutively and inducibly expressed in immune response elements such as T cells, macrophages and neutrophils. (nih.gov)
  • 2. Imaging-based methods for assessing caspase activity in single cells. (nih.gov)
  • For this purpose, the idea that adding different side chains to the anthraquinone skeleton will increase its therapeutic effects and that new anthraquinone derivatives can prevent the development of resistance in cancer cells has gained importance [ 5 , 6 ]. (hindawi.com)
  • Nod1-deficient breast cancer cells (MCF-7) were more resistant to tumor necrosis factor-induced cytotoxicity, and this was accompanied by a reduction in caspase signaling. (biomedcentral.com)
  • 8. Pro-caspase-3 is a major physiologic target of caspase-8. (nih.gov)
  • Association with another p18/p10 heterodimer generates active caspase-8. (rndsystems.com)
  • Recently, several studies have shown that microvascular thrombosis generation also plays a pivotal role in the pathophysiology of AKI, and many antithrombin agents, such as heparin [ 6 ] and antithrombin III (ATIII) [ 7 - 9 ] could mitigate renal IRI. (oncotarget.com)
  • The FLICA reagent FAM-LETD-FMK enters each cell and irreversibly binds to activated caspase-8. (immunochemistry.com)
  • 13. Caspases from scleractinian coral show unique regulatory features. (nih.gov)