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 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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A 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.
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
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.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
A 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)
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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
A prokaryotic ATP-dependent protease that plays a role in the degradation of many abnormal proteins. It is a tetramer of 87-kDa subunits, each of which contains a proteolytic site and a ATP-binding site.
Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. They are usually comprised of large multi-subunit assemblies. The domains can occur within a single peptide chain or on distinct subunits.
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.
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.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
Established cell cultures that have the potential to propagate indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
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)
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.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
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 cell line derived from cultured tumor cells.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
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 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.
Proteins prepared by recombinant DNA technology.
Peptides composed of between two and twelve amino acids.
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
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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 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.
Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.
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.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
The rate dynamics in chemical or physical systems.
An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Physiologically inactive substances that can be converted to active enzymes.
The process of cleaving a chemical compound by the addition of a molecule of water.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides.
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.
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 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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
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.
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
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.
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 serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
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.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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.
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 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.
Elements of limited time intervals, contributing to particular results or situations.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The sum of the weight of all the atoms in a molecule.
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.
A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.)
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.
Proteins found in any species of bacterium.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.

C. elegans MAC-1, an essential member of the AAA family of ATPases, can bind CED-4 and prevent cell death. (1/406)

In the nematode Caenorhabditis elegans, CED-4 plays a central role in the regulation of programmed cell death. To identify proteins with essential or pleiotropic activities that might also regulate cell death, we used the yeast two-hybrid system to screen for CED-4-binding proteins. We identified MAC-1, a member of the AAA family of ATPases that is similar to Smallminded of Drosophila. Immunoprecipitation studies confirm that MAC-1 interacts with CED-4, and also with Apaf-1, the mammalian homologue of CED-4. Furthermore, MAC-1 can form a multi-protein complex that also includes CED-3 or CED-9. A MAC-1 transgene under the control of a heat shock promoter prevents some natural cell deaths in C. elegans, and this protection is enhanced in a ced-9(n1950sd)/+ genetic background. We observe a similar effect in mammalian cells, where expression of MAC-1 can prevent CED-4 and CED-3 from inducing apoptosis. Finally, mac-1 is an essential gene, since inactivation by RNA-mediated interference causes worms to arrest early in larval development. This arrest is similar to that observed in Smallminded mutants, but is not related to the ability of MAC-1 to bind CED-4, since it still occurs in ced-3 or ced-4 null mutants. These results suggest that MAC-1 identifies a new class of proteins that are essential for development, and which might regulate cell death in specific circumstances.  (+info)

Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. (2/406)

The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development.  (+info)

CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. (3/406)

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

mE10, a novel caspase recruitment domain-containing proapoptotic molecule. (4/406)

Apoptotic signaling is mediated by homophilic interactions between conserved domains present in components of the death pathway. The death domain, death effector domain, and caspase recruitment domain (CARD) are examples of such interaction motifs. We have identified a novel mammalian CARD-containing adaptor molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits significant homology (47% identity and 64% similarity) to the CARD of a gene from Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis indicates that CARD-mediated mE10 oligomerization is essential for killing activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and promoted its processing to the active dimeric species. Taken together, these data suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by mE10-induced oligomerization.  (+info)

Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1. (5/406)

Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This is despite indications that remnant apoptotic events are detected following exercise, muscle injury and the progression of dystrophinopathies. The recent elicitation of a cytochrome c-mediated induction of caspases has led to speculation regarding a cytochrome c mechanism in muscle. We demonstrate that cytosols from skeletal muscle biopsies from healthy human volunteers lack the ability to activate type-II caspases by a cytochrome c-mediated pathway despite the confirmed presence of both procaspase-3 and -9. This was not due to the presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase activity when added to a control cytosol, subsequently activated by cytochrome c and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These data indicate that human skeletal muscle cells will be refractory to mitochondrial-mediated events leading to apoptosis and thus can escape a major pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation of cell survival in the presence of the profusion of mitochondria required for energy generation in motility.  (+info)

An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. (6/406)

We report here the reconstitution of the de novo procaspase-9 activation pathway using highly purified cytochrome c, recombinant APAF-1, and recombinant procaspase-9. APAF-1 binds and hydrolyzes ATP or dATP to ADP or dADP, respectively. The hydrolysis of ATP/dATP and the binding of cytochrome c promote APAF-1 oligomerization, forming a large multimeric APAF-1.cytochrome c complex. Such a complex can be isolated using gel filtration chromatography and is by itself sufficient to recruit and activate procaspase-9. The stoichiometric ratio of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated, caspase-9 disassociates from the complex and becomes available to cleave and activate downstream caspases such as caspase-3.  (+info)

Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. (7/406)

The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-kappaB activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-kappaB and apoptotic signaling pathways and may be a component of the host innate immune response.  (+info)

Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. (8/406)

Mistletoe lectin I (ML-I) is a major active component in plant extracts of Viscum album that is increasingly used in adjuvant cancer therapy. ML-I exerts potent immunomodulating and cytotoxic effects, although its mechanism of action is largely unknown. We show that treatment of leukemic T- and B-cell lines with ML-I induced apoptosis, which required the prior activation of proteases of the caspase family. The involvement of caspases is demonstrated because (a) a peptide caspase inhibitor almost completely prevented ML-I-induced cell death and (b) proteolytic activation of caspase-8, caspase-9, and caspase-3 was observed. Because caspase-8 has been implicated as a regulator of apoptosis mediated by death receptors, we further investigated a potential receptor involvement in ML-I-induced effects. Cell death triggered by ML-I was neither attenuated in cell clones resistant to CD95 nor in cells that were rendered refractory to other death receptors by overexpressing a dominant-negative FADD mutant. In contrast, ML-I triggered a receptor-independent mitochondria-controlled apoptotic pathway because it rapidly induced the release of cytochrome c into the cytosol. Because ML-I was also observed to enhance the cytotoxic effect of chemotherapeutic drugs, these data may provide a molecular basis for clinical trials using MLs in anticancer therapy.  (+info)

According to biochemical assays, the Bcl-2 protein Diva from mouse regulates programmed cell death by heterodimerizing with other members of the family and by interacting with the apoptotic protease-activating factor Apaf-1. In typical Bcl-2 heterodimers, peptide fragments comprising the Bcl-2 homology domain 3 (BH3 domain) of proapoptotic members are capable of forming functional complexes with prosurvival proteins. High-resolution structural studies have revealed that the BH3 peptide forms an α-helix positioned in a canonical hydrophobic cleft of the antiapoptotic protein. Because Diva shows mutations in conserved residues within this area, it has been proposed to have a different interacting surface. However, we showed previously that Diva binds through the canonical groove the BH3 peptide of the human Bcl-2 killing member Harakiri. To further test Divas binding capabilities, here we show Nuclear Magnetic Resonance (NMR) data, indicating that Diva binds peptides derived from the BH3 domain ...
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APAF1兔多克隆抗体(ab2001)可与小鼠, 大鼠, 人样本反应并经WB, IHC, ICC/IF实验严格验证,被7篇文献引用。所有产品均提供质保服务,中国75%以上现货。
Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a molecular timer that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may ...
Because neither E2F1 overexpression nor derepression with the addition of TSA alone was able to induce Apaf-1 up-regulation in mature neurons (Figs. 4 c and 5 a), we hypothesized that this region of chromatin may be highly repressed in mature neurons. Indeed, expression of E2F1 in the presence of TSA induced a marked transcriptional increase in Apaf-1 (Fig. 5 c) and rendered mature P28 neurons sensitive to cytochrome c (Fig. 5 d). This sensitivity of P28 neurons was dependent on the up-regulation of Apaf-1, as neurons isolated from Apaf-1-deficient mice failed to undergo cytochrome c-induced apoptosis after TSA and E2F1 treatment (Fig. 5 e). These data support the model that neuronal maturation is accompanied by increased repression of Apaf-1 at the level of chromatin structure.. We tested this model directly with a chromatin immunoprecipitation (ChIP) assay using antibodies to acetylated histone 3 (AcH3), which is indicative of active chromatin, and histone 3 trimethylated on lysine 9 (MeH3K9), ...
Detailed annotation info for ENST00000348549; Caspase-9 precursor (EC 3.4.22.-) (CASP-9) (ICE-like apoptotic protease 6) (ICE-LAP6) (Apoptotic protease Mch-6) (Apoptotic protease activating factor 3) (APAF-3). [Source:Uniprot/SWISSPROT;Acc:P55211 ...
Expression of APAF1 (APAF-1, CED4) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
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When it comes to traveling in a car with your dog, safety should be paramount for you both. However, a recent study from Volvo Car USA found some surprising statistics. ...
While all signs had pointed to a Bellator partnership with FX in 2011, the promotion on Tuesday jointly announced a three-year deal to air on MTV2.
Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the ca …
The invention relates to an isolated nucleic acid molecule encoding a caspase-14 polypeptide or functional fragment thereof, a vector that contains the nucleic acid molecule and a host cell that contains the vector. The invention also relates to an isolated gene encoding caspase-14, as well as functional fragments thereof. The gene or nucleic acid molecule can include single or double stranded nucleic acids corresponding to coding or non-coding strands of the caspase-14 nucleotide sequence. Isolated caspase-14 polypeptides or functional fragments thereof are also provided, as are antibodies that specifically bind thereto. In addition, the invention relates to methods of identifying compounds that modulate caspase-14 activity.
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 ...
CARD8 (caspase recruitment domain family, member 8), Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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Apoptotic signaling is altered at many loci in cancer cells. Although many tumors develop resistance to cytochrome c-induced apoptosis, we have discovered that breast cancer cells exhibit a unique hypersensitivity to cytochrome c-induced apoptosis. Interestingly, this sensitivity is not due to changes in core apoptosomal proteins ( 44) but is due to a PHAPI-mediated posttranslational event that enhances the recruitment of caspase-9 to the Apaf-1 CARD. These findings have the potential to affect breast cancer chemotherapy through the development of apoptosome activators or cytochrome c mimetics as shown, in principle, by the fact that malignant mammary epithelial cells could be more easily killed by cytosolic cytochrome c than their normal counterparts.. PHAPI-mediated increase in caspase activation in breast cancer. Whereas many inhibitory signaling pathways converge on the apoptosome, there are very few physiologic/pathologic examples of enhanced apoptosome activation. Our data suggest that ...
The effect was found to be associated with increased expression of E2F-1 in cervical cancer cells as there is no CAPE-mediated induction of E2F-1 in the precancerous cervical Z172 cells. CAPE also upregulated the E2F-1 target genes cyclin A, cyclin E, and apoptotic protease activation of factor 1 (Apaf-1) but down regulated cyclin B and myeloid leukemia cell differentiation protein (Mcl-1). These results suggested the involvement of E2F-1 in CAPE-mediated growth inhibition and cell cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered transcriptional activity of the apaf-1 and mcl-1 promoters. Further studies using chromatin immunoprecipitation (ChIP) assays demonstrated that in CAPE-treated cells, E2F-1 binding to the apaf-1 and cyclin B promoters was increased and decreased, respectively. Furthermore, E2F-1 silencing abolished CAPE-mediated effects on cell cycle arrest, apoptosis, and related gene expression ...
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Objetivou-se caracterizar clinicamente a Doença Inflamatória de Vias Aéreas (DIVA) assim como verificar o comportamento da atividade dos macrófagos alveolares destes animais. Utilizaram-se 17 eqüinos adultos...
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The present study examined levels of various components of the cell death machinery and drug sensitivity of 60 human cancer cell lines to anticancer drugs. With the exception of procaspase-3, which was undetectable in MCF-7 cells, caspases-2, -3, -6, -7, -8, and -9, as well as Apaf-1, were detectable in all 60 cell lines. Although these components of the cell death machinery varied widely in abundance, strong correlations between levels of Apaf-1 or procaspase-2, -3, -6, -8, or -9 and sensitivity to any class of antineoplastic agent were not observed. These results, although negative, have several important implications.. The attempt to correlate drug sensitivity with levels of various components of the cell death machinery was prompted by previous studies indicating that drug-induced apoptosis is markedly diminished when certain key components of the core cell-death machinery, particularly Apaf-1, procaspase-9, or procaspase-3, are genetically or functionally deleted (36, 37, 38 , 58 , 88 , 99) ...
Diva (death inducer binding to vBcl-2 and Apaf-1) is a Bcl-2 family member, and has been reported to play roles in apoptosis and oocyte maturation. Diva has also been shown to interact with Nm23-H2/NDPK B, which is involved in cellular differentiation. The main aim of this study was to elucidate the function and possible mechanisms for Diva in cellular differentiation in the brain. In the present study, in PC-12 cells, Diva expression was decreased after differentiation and reciprocally, NDPK B expression was increased and it translocated into the nucleus. Endogenous Diva was also shown to interact with both ß-tubulin and NDPK B. Overexpression of Diva in PC-12 cells did not change the expression level of NDPK B, but inhibited its nuclear localization. Diva-overexpressing cells had a decreased percentage of differentiated cells and average neurite length was shortened. This was due to the formation of more Diva/NDPK B and Diva/ß-tubulin complexes, at the expense of NDPK B/ß-tubulin complexes. ...
Chris Cory is currently on a nationwide tour with DIVA DOG, partnering with animal rescue groups and pit bull advocacy organizations. So far, we have brought DIVA DOGs message to LA, Philadelphia, Portland (OR), Kansas City, Fredericksburg (VA) and now Toronto. We are starting to go international! Hoping to bring DIVA DOG to the UK by Labor Day.. The next stops on the DIVA DOG tour are Montclair (NJ), NYC and Birmingham(AL). Woo-hoo! All upcoming events info is in our Monthly Newsletter/E-Zine. Keep on the lookout for some new and exciting DIVA DOG events in July and August to commemorate Coral the Diva Dogs birthday July 23. We will be working with a wonderful rescue called Mariahs Promise in Colorado and bringing DIVA DOG right to the Denver area, where BSL (breed-specific legislation) is really destroying homes and families, as pit bulls are ripped from their families based soley upon their breed. To learn more about the seriousness of this issue and how BSL is something that MUST be ...
Chris Cory is currently on a nationwide tour with DIVA DOG, partnering with animal rescue groups and pit bull advocacy organizations. So far, we have brought DIVA DOGs message to LA, Philadelphia, Portland (OR), Kansas City, Fredericksburg (VA) and now Toronto. We are starting to go international! Hoping to bring DIVA DOG to the UK by Labor Day.. The next stops on the DIVA DOG tour are Montclair (NJ), NYC and Birmingham(AL). Woo-hoo! All upcoming events info is in our Monthly Newsletter/E-Zine. Keep on the lookout for some new and exciting DIVA DOG events in July and August to commemorate Coral the Diva Dogs birthday July 23. We will be working with a wonderful rescue called Mariahs Promise in Colorado and bringing DIVA DOG right to the Denver area, where BSL (breed-specific legislation) is really destroying homes and families, as pit bulls are ripped from their families based soley upon their breed. To learn more about the seriousness of this issue and how BSL is something that MUST be ...
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CARD9 antibody [N1N3] (caspase recruitment domain family, member 9) for IHC-P, WB. Anti-CARD9 pAb (GTX110789) is tested in Human, Mouse samples. 100% Ab-Assurance.
Curators comment: (updated: 22 Mar 2007 23:30:25 GMT). The simulation image shown corresponds to active caspase-3 temporal evolution for Apaf-1 concentration of 20nM as depicted in Fig-2A of the paper. Result obtained from MathSBML.. ...
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The apoptosome is the cellular structure that facilitates programmed cell death. A new 3D map of it lays groundwork for future drug development.
14-3-3 tau mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. 14-3-3 tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage ...
Expression of CASP9 (APAF-3, ICE-LAP6, MCH6, PPP1R56) in vagina tissue. Antibody staining with HPA001473, HPA046488 and CAB004348 in immunohistochemistry.
Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signalling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced ...
Proteasome inhibitors including bortezomib have attracted considerable attention as potential anticancer agents, but the mechanism(s) by which proteasome inhibitors induce apoptosis is poorly understood. In the present study, we provided evidence using the human Jurkat T-cell leukemic cell line with or without stable silencing of the key adaptor protein, Apaf-1, that bortezomib-induced apoptosis but not Fas (death receptor)-mediated apoptosis is dependent on Apaf-1 expression. Furthermore, we noted that expression of Apaf-1 was variable in a panel of pediatric ALL patient samples, and Apaf-1 expression was absent altogether in one patient. The primary cells presented with a high degree of spontaneous apoptosis upon ex vivo culture; however, the Apaf-1-deficient sample presented the lowest sensitivity toward bortezomib-induced apoptosis, thus providing correlative evidence for a role of Apaf-1 in bortezomib-induced cell killing (defects in other apoptosis signaling pathways may also come into ...
As previously reported, recombinant xEIAP/XLX is rapidly degraded by at least two distinct, consecutively acting proteolytic systems [11, 14]. Within 2 h incubation, xEIAP/XLX is significantly degraded in both CSF-arrested and interphase egg extracts in a C-terminal RING finger-dependent manner. Subsequently, spontaneous cytochrome c-induced caspase activation begins after 4 h incubation in interphase egg extracts (apoptotic egg extracts), and the remaining xEIAP/XLX is cleaved by the activated caspases at yet unidentified site(s). This caspase activation is delayed or suppressed in CSF-arrested egg extracts by a p42MAPK-dependent pathway [7-11]. We found that the electrophoretic mobilities of recombinant 6XHis-tagged (6XHis-FL) and MBP-tagged (MBP-FL) xEIAP/XLX slightly decreased during incubation in CSF-arrested but not interphase egg extracts (Fig. 1B), whereas those of other BIR family proteins (xSurvivin1/xBIR1, xSurvivin2/SIX, and xXIAP) did not (data not shown). However, the rapid ...
Complete information for CARD10 gene (Protein Coding), Caspase Recruitment Domain Family Member 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
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Här presenteras refereegranskade artiklar i tidskrifter författade av institutionens anställda, som har publicerats under innevarande och föregående kalenderår. Uppgifterna är hämtade från databasen DIVA.. ...
Most drug discovery efforts focus on generating inhibitors leading to loss-of-function phenotypes. My lab has been focusing on discovering ways to activate enzymes leading to gain-of-function phenotypes. Many enzymes such as proteases and kinases are stored in dormant off forms that are subsequently activated through post-translational modification. Work will be presented for discovery of small molecule activators for the apoptotic proteases known as caspases, as well a Ser-Thr kinase PDK-1. Our group is also developing split-proteins that can be activated by orthogonal small molecule dimerizers to phenocopy the effects seen from the small molecule activators. Such protein activators allow one to ignite signaling from specific nodes and thus probe the sufficiency of enzyme activity to drive a cellular response. Protein activation, as opposed to inhibition, expands the landscape for drug discovery.. Citation Format: James A. Wells, Dennis Wolan, Julie Zorn, Debajyoti Datta, Daniel Gray, Jack ...
Units: umol/l. Method: spatial interpolation produced with DIVA (Data-Interpolating Variational Analysis). URL: http://modb.oce.ulg.ac.be/DIVA. Comment: Every year of the time dimension corresponds to a 10-year centred average for the autumn season (Sep-Nov). Diva settings: Snr=1.0, CL=0.7 ...
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LUPUS AND ME I am a soon-to-be 30-something (currently on a 2-week countdown) latina jew who has been diagnosed officially with lupus for three two one years. I am one of those many cases that should have been diagnosed years before. Here is what gave the final clue to the lupus diagnosis: I started feeling like death warmed-over…
Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated ... with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. ... not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti- ... Kondaveeti S, Hibberd ML, Booy R, Nadel S, Levin M (1999). "Effect of the Factor V Leiden mutation on the severity of ...
... apoptotic protease activating factor 1) upon mitochondria-mediated apoptosis which must be stimulated by some type of stress ... c-dependent caspase activation in ovarian cancer cell lines due to diminished or absent apoptotic protease activating factor-1 ... Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis ... By activating the apoptosome by an outside stimulus apoptosis can occur and get rid of the mutated cells. Numerous approaches ...
Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1).[5] ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 ... Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... intrinsic apoptotic signaling pathway. • activation of cysteine-type endopeptidase activity involved in apoptotic process by ...
Knockout or inhibition of apoptotic protease activating factor 1 (APAF1), also results in malformations and increased embryonic ... An atrophic factor is a force that causes a cell to die. Only natural forces on the cell are considered to be atrophic factors ... Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ... Solomon M, Belenghi B, Delledonne M, Menachem E, Levine A (1999). "The involvement of cysteine proteases and protease inhibitor ...
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate ... Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C.[81] Pathological inactivation of apoptosis ...
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate ... Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C.[80] Pathological inactivation of apoptosis ... There also exists a caspase-independent apoptotic pathway that is mediated by AIF (apoptosis-inducing factor).[43] ...
1996). "Mch3, a novel human apoptotic cysteine protease highly related to CPP32". Cancer Res. 55 (24): 6045-52. PMID 8521391. ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ... Zheng, L; Schickling O; Peter M E; Lenardo M J (August 2001). "The death effector domain-associated factor plays distinct ... a novel human apoptotic cysteine protease containing two FADD-like domains". Proc Natl Acad Sci USA. 93 (15): 7464-9. Bibcode: ...
... proteases, and thus the apoptotic cascade. Additional sources of neuronal cell death related to excitotoxicity involve energy ... including activating and inactivating certain K+ channels. Epinephrine is found in the lateral tegmental system, medulla, ... Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, ... ions into the postsynaptic cell through ion channels activated by neurotransmitter binding. There are two different kinds of ...
... by activating pro-apoptotic factors. Other researchers contend that it is not mitochondrial membrane rupture that leads to ... and which can activate harmful calcium-dependent proteases such as calpain. Reactive oxygen species (ROS) are also produced as ... Other factors that increase the likelihood that the MPTP will be induced include the presence of certain fatty acids, and ... Various factors enhance the likelihood of MPTP opening. In some mitochondria, such as those in the central nervous system, high ...
regulation of epidermal growth factor-activated receptor activity. • regulation of growth. • Ras protein signal transduction. • ... When the coagulated protease-activated protein C inhibits p66SHC a cytoprotective effect on diabetic nephropathy is placed on ... negative regulation of apoptotic process. • positive regulation of MAPK cascade. • negative regulation of transcription, DNA- ... epidermal growth factor receptor signaling pathway. • cellular response to growth factor stimulus. • MAPK cascade. • Fc-epsilon ...
... activating transcription factor 4) and uniquely responsive to ER stress. CHOP causes downregulation of the anti-apoptotic ... where it is cleaved by proteases to form an active 50kDa transcription factor that translocates to the nucleus. It binds to ... The activated domain is able to activate the transcription factor XBP1(Xbox binding protein) mRNA (the mammalian equivalent of ... ATF6 (activating transcription factor 6) is a basic leucine zipper transcription factor. Upon Grp78 dissociation, the entire ...
Once activated, the T cells release pro-inflammatory cytokines and chemokines. The interactions with TCRs are characterized by ... Some studies have reported increased protease levels in strains that cause scarlet fever in comparison to those associated with ... The receptor-binding pathway and Fas-mediated apoptotic signaling pathway have been implicated in this process. The induction ... Each step is tightly regulated by multiple factors, allowing sophisticated temporal expression of the mature proteinase. SpeA ...
TRAIL-activated apoptotic signaling pathway. • proteolysis. • macrophage differentiation. • TRIF-dependent toll-like receptor ... cysteine-type endopeptidase activity involved in apoptotic process. • tumor necrosis factor receptor binding. • cysteine-type ... Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. ... apoptotic process. • extrinsic apoptotic signaling pathway. • negative regulation of extrinsic apoptotic signaling pathway via ...
... but they are all still able to cross present antigens in order to activate cytotoxic CD8+ T cells. There are many factors that ... pDCs are found within the blood and are able to cross present antigens directly or from neighboring apoptotic cells, but the ... where an increasingly acidic environment along with the activation of enzymes such as lysosomal proteases triggers the ... After vaccine induced activation, dendritic cells are able to migrate to lymph nodes and activate CD4+ T helper cells as well ...
FAS/FAS-L system - expression of Fas ligand (Fas-L) on the surface of SCs activates apoptotic death of Fas receptor bearing ... Protease inhibitor-9 (PI-9) - member of serpin family (serine protease inhibitors) - induces secretion of protease Granyzme B, ... Besides expressing factors that are crucial for sperm cell maturation, Sertoli cells are producing a wide range of molecules ( ... During male development, the gene SRY activates SOX9, which then activates and forms a feedforward loop with FGF9. Sertoli cell ...
The activity of different CDKs activate cell signaling pathways and transcription factors that regulate key events in mitosis ... Activation of p53 can lead to cell cycle arrest, which can be reversed under some circumstances, or apoptotic cell death. This ... ATP-binding cassette transporter Arginine phosphorylation by McsB kinase marks proteins for degradation by a Clp protease. The ... Protein kinase N1 is responsible for the phosphorylation of the TNF receptor-associated factor (TRAF1) on serine 139 under ...
The activated C1r then cleaves and activates the serine protease C1s. The activated C1s cleaves C4 into C4a and C4b, and C2 ... Among the many functions of C1q, C1q triggers clearance of immune complexes and apoptotic cells by activating the classical ... In the absence of these activation factors, C1q is part of the inactive C1 complex which consists of six molecules of C1q, two ... The classical complement pathway can also be activated by apoptotic cells, necrotic cells, and acute phase proteins. The ...
Activated STAT5 dimers are, however, short-lived and the dimers are made to undergo rapid deactivation. Deactivation may be ... For example, mutations may lead to increased expression of anti-apoptotic genes, the products of which actively prevent cell ... Indirect inhibition targets kinases associated with STAT5, or targets proteases that carry out terminal truncation of proteins ... Cytokine Growth Factor Rev. 10 (2): 131-57. doi:10.1016/S1359-6101(99)00011-8. PMID 10743504.. .mw-parser-output cite.citation{ ...
positive regulation of apoptotic process. • nerve growth factor processing. • extrinsic apoptotic signaling pathway via death ... are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. The activated transcription factor c- ... This form of NGF is also referred to as proNGF (NGF precursor). The gamma subunit of this complex acts as a serine protease, ... nerve growth factor receptor binding. • growth factor activity. • receptor binding. Cellular component. • endosome. • Golgi ...
... nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), v-raf murine sarcoma viral oncogene homolog B1 (B-Raf ... Preliminary docking studies indicate that chalcones may inhibit SARS-CoV-2 proteins specifically the main protease (Mpro), RNA ... "Antiproliferative and pro-apoptotic activities of 2′- and 4′-aminochalcones against tumor canine cells" (PDF). European Journal ... vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) kinase, matrix ...
Apoptotic death similar to that found in animals does not occur in plants, due to the cell wall of plant cells preventing ... The group used human insulin-like growth factor 1 receptor (IGF-1R) to stimulate cell death in 293T cells and mouse embryonic ... Rh2 also induces increase ROS levels, which activate the NF-κB signaling pathway, while blocking ROS with NAC or catalase ... various other proteases. These substances are "danger signals" and result in inflammation. While certain templates of ...
Involvement of chemokines, such as SDF1 (CXCL12), the fibroblast growth factor (FGF), and the transforming growth factor β (TGF ... The use of antibodies that block integrins or protease inhibitors in clinical trials leads to the emergence of tumor cells with ... It is also the fact that moving tumor cells display increased activity of anti-apoptotic genes, which causes resistance to ... The binding to receptors activates a signaling pathway involving some proteins of the small GTPase system (Cdc42, Rac, RhoA, ...
Protease inhibitors are another group of drugs (e.g. ritonavir) and some of them can cause a range of problems such as: ... Cellular basis for the negative inotropic effect of tumor necrosis factor alpha in the adult mammalian heart. J Clin Invest ... and cytokine apoptotic signaling. Cardiovasc Toxicol 2004;4:97-107. Twu C, Liu QN, Popik W, et al. Cardiomyocytes undergo ... Alternatively, the immunoglobulins can reduce the effects or secretions of cytokines and cellular growth factors. Signs and ...
... microvesicles can induce clotting by binding to clotting factors or by inducing the expression of clotting factors in other ... And the last one is cell death leading to apoptotic blebbing. These are all energy-requiring processes. Under physiologic ... In the late stage, the extent of inflammation correlates with numbers of activated macrophages that contribute to joint ... Synthesis of reactive oxygen species, proteases, and prostaglandins by neutrophils is increased. Activation of platelets via ...
The JAK/STAT pathway moderates many of these effectors by activating STATs, which are transcription factors with the ability to ... The function of these pro-apoptotic proteins, however, is impaired, and apoptosis is not carried out in these cells. BCR-ABL ... have also been identified in downregulating BCR-ABL kinase translation and promoting its degradation by protease.[23][24] ... BCR-ABL fusion cells also exhibit constitutively high levels of activated Ras bound to GTP, activating a Ras-dependent ...
Extrinsic apoptotic pathways: Occur when factors outside the cell activate cell surface death receptors (e.g., Fas) that result ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. There are two types of caspases: ... Risk factor[edit]. The greatest risk factor for neurodegenerative diseases is aging. Mitochondrial DNA mutations as well as ... This activates the effectors that in turn cleave other proteins resulting in apoptotic initiation.[3] ...
Specifically, mannose binding triggers recruitment of MBL-associated serine proteases (MASPs). The serine proteases activate ... and single stranded RNA which recruit factors via twin N-terminal CARD domains to activate antiviral gene programs, which may ... Ting JP, Williams KL (April 2005). "The CATERPILLER family: an ancient family of immune/apoptotic proteins". Clinical ... NLRP3 can be activated and give rise to NLRP3 inflammasome by ATP, bacterial pore-forming toxins, alum and crystals. Alongside ...
... due to a lower concentration of lysosomal proteases and even the presence of protease inhibitors. ... Listeriolysin is activated by the acidic environment of the phagosome.[33] In addition, Listeria secrete two phospholipase C ... Pathogen-infected apoptotic cells will trigger inflammation, but damaged cells that are degraded as part of the normal tissue ... which is hypothesised to prevent membrane recycling and recruitment of fusion factors, so the phagosome does not fuse with ...
extrinsic apoptotic signaling pathway via death domain receptors. • TRAIL-activated apoptotic signaling pathway. • cellular ... protease binding. • receptor activity. • death receptor activity. • protein binding. • transcription factor binding. ... Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a (неопр.). *↑ Miyazaki, T; Reed J C. A GTP-binding ... apoptotic process. • signal transduction. • activation of NF-kappaB-inducing kinase activity. • ...
Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF ... the release of proinflammatory mediators and proteases by mast cells, and. *perturbations in the innate immune response that ... Liquefaction degeneration of the basal layer with apoptotic keratinocytes (referred to as Civatte, colloid, hyaline, or cytoid ... activates CD8+ T cells on keratinocytes or by encounters with activated CD4+ helper T cells or cytokines produced by activated ...
regulation of epidermal growth factor-activated receptor activity. • regulation of resting membrane potential. • regulation of ... apoptotic process. • activation of MAPKK activity. • thymus development. • positive regulation of coagulation. • negative ... such that they either directly regulate gamma secretase activity or themselves are protease enzymes. Multiple alternatively ... negative regulation of epidermal growth factor-activated receptor activity. • cell adhesion. • hematopoietic progenitor cell ...
transcription factor binding. • activating transcription factor binding. • rRNA binding. • protein N-terminus binding. • ... negative regulation of apoptotic process. • regulation of DNA damage response, signal transduction by p53 class mediator. • ... 2008). «Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases.». J Cell ... positive regulation of NF-kappaB transcription factor activity. • protein oligomerization. • negative regulation of protein ...
Due to its role in generating the activated form of NF-κB, an anti-apoptotic and pro-inflammatory regulator of cytokine ... Degradation of Aux/IAA proteins derepresses transcription factors in the auxin-response factor (ARF) family and induces ARF- ... See also: threonine protease § mechanism. The proteasome functions as an endoprotease.[64][65][66][67] The mechanism of ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ...
... in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis". Gene 488 (1-2 ... funcionando como un factor de transcrición,[12][13] e actividades antimicrobianas (potencialmente asociadas con actividades ... necesítase un composto que poida bloquear o sitio activo das aspartil proteases e que poida atravesar a barreira ... "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science 286 ( ...
... which then activates JNK. JNK translocates to the nucleus and activates transcription factors such as c-Jun and ATF2. The JNK ... protease binding. • tumor necrosis factor receptor binding. • cytokine activity. • identical protein binding. ... activation of cysteine-type endopeptidase activity involved in apoptotic process. • tumor necrosis factor-mediated signaling ... TNF, DIF, TNF-alpha, TNFA, TNFSF2, Tumour necrosis factor, TNF-α, tumor necrosis factor, TNLG1F, Tumor necrosis factor alpha. ...
negative regulation of activated T cell proliferation. • cellular response to drug. • cell cycle arrest. • learning or memory. ... The protein can exist in multiple isoforms, the normal PrPC and protease-resistant forms designated PrPRes such as the disease- ... negative regulation of apoptotic process. • response to oxidative stress. • negative regulation of sequence-specific DNA ... This can arise from genetic factors, infection from external source, or spontaneously for reasons unknown. Accumulation of PrP ...
... regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling ... negative regulation of apoptotic process. • regulation of branching involved in salivary gland morphogenesis by mesenchymal- ... It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta- ... Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is ...
... s (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of ... There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in ... Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. ... Creagh, Emma M. (December 2014). "Caspase crosstalk: integration of apoptotic and innate immune signalling pathways". Trends in ...
nuclear fragmentation involved in apoptotic nuclear change. • positive regulation of endothelial cell apoptotic process. • ... adenylate cyclase-activating G-protein coupled receptor signaling pathway. • modulation of chemical synaptic transmission. ... cellular response to tumor necrosis factor. • cellular response to estradiol stimulus. • cellular response to peptide hormone ... apoptotic process. • positive regulation of cAMP biosynthetic process. • negative regulation of fat cell differentiation. • ...
protease binding. • platelet-derived growth factor receptor binding. • GO:0001948 protein binding. • identical protein binding ... apoptotic cell clearance. • regulation of postsynaptic neurotransmitter receptor internalization. • regulation of protein ... "The phosphotyrosine binding-like domain of talin activates integrins". J. Biol. Chem. 277 (24): 21749-58. doi:10.1074/jbc. ... fibroblast growth factor binding. • insulin-like growth factor I binding. • C-X3-C chemokine binding. • integrin binding. • ...
Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of ... There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in ... Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. ...
transforming growth factor beta receptor binding. • growth factor activity. • GO:0001948 protein binding. ... regulation of apoptotic process. • skeletal system development. • palate development. • ureteric bud development. • regulation ... GDF11 also activates the Smad2/3 phosphorylation pathway in skin endothelial cells and improves skin vasculature.[17] ... protease inhibitor, and NTR domains.[43] WFIKKN2 has a high affinity for GDF11, and previously has been found to inhibit the ...
Once activated, they change shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens. ... Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase ... "Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes". Infect. Immun. 79 (11): ... "ITAM signaling by Vav family Rho guanine nucleotide exchange factors regulates interstitial transit rates of neutrophils in ...
Phagocytes further release proteases that break down the ECM of neighbouring tissue, freeing the activated fibroblasts to ... Overview of involved growth factorsEdit. Following are the main growth factors involved in wound healing: Growth factor. ... in addition to their role in host defense and in the clearance of apoptotic cells, are being increasingly recognized for their ... Factors affecting wound healingEdit. Many factors controlling the efficacy, speed, and manner of wound healing fall under two ...
The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin ... and eventually activating the transcription factor NF-κB. A nuclear localisation signal on the NF-κB protein allows it to be ... There they serve as transcription factors when bound to their ligand; in the absence of a ligand, many such receptors function ... Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity.[15] ...
transcription factor binding. • RNA polymerase II activating transcription factor binding. • phosphoprotein binding. • kinase ... hepatocyte apoptotic process. • apoptotic process. • positive regulation of transcription regulatory region DNA binding. • ... Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the ... transcription factor complex. • spindle. • cyclin/CDK positive transcription elongation factor complex. • chromatin. • cell ...
protease binding. • protein self-association. • peptidase activity. • protein binding. • kinase activator activity. • cysteine- ... regulation of apoptotic process. • defense response. • regulation of T cell receptor signaling pathway. • negative regulation ... It has an important role in the activation of the transcription factor NF-κB, in the production of interleukin-2 (IL-2) and in ... Cells expressing an uncleavable A20 mutant is however still capable to activate NF-κB, but cells expressing the C-terminal or ...
negative regulation of apoptotic process. • positive regulation of release of sequestered calcium ion into cytosol. • D- ... accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated ... Growth factor. See here instead.. Insulin. *Agonists: Chaetochromin (4548-G05). *Insulin-like growth factor 1 ... positive regulation of apoptotic process. • negative regulation of release of sequestered calcium ion into cytosol. • positive ...
In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. ... peroxisome proliferator activated receptor binding. • ubiquitin binding. Cellular component. • cytosol. • endocytic vesicle ... negative regulation of apoptotic process. • cellular response to organic substance. • cellular response to hydrogen peroxide. • ... Mdm2 also interacts with a ubiquitin specific protease, USP7, which can reverse Mdm2-ubiquitylation and prevent it from being ...
Apoptotic protease activating factor antibody. *Apoptotic protease-activating factor 1 antibody. *CED 4 antibody ... Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs.. Mol Cell Biol 28:40 ... Lane 1 : K562 cell lysate in absence of blocking peptide. Lane 2 : K562 cell lysate in presence of blocking peptide.. Observed ... Apoptotic protease activating factor 1 antibody. * ... Use a concentration of 1 µg/ml. ICC/IF. Use a concentration of ...
apoptotic protease activating factor 1. 0.014. atp2b4. ATPase, Ca++ transporting, plasma membrane 4. 0.014. ... guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O, a. 0.019. ... ogt.1. O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase ...
Apoptotic protease activating factor 1 (Apaf-1). Homo sapiens. ENSEMBL: ENSG00000120868 proto-oncogene c-fos. Homo sapiens. ... Apoptotic protease activating factor (Apaf-1) 5UTR mRNA. Homo sapiens. UTRef: 5HSAR027754 [U1] ... Apoptotic protease activating factor (Apaf-1) mRNA. Homo sapiens. RefSeq: NM_001160 [T1] ... Protein factor requirements of the Apaf-1 internal ribosome entry segment: roles of polypyrimidine tract binding protein and ...
Growth factor withdrawal activates GSK3b, which phosphorylates cyclin D, leading to its rapid ubiquitination and proteosomal ... The caspases convey the apoptotic signal in a proteolytic cascade, with caspases cleaving and activating other caspases that ... a protease released from mitochondria. Activated Apaf-1 activates caspase-9 and the rest of the caspase cascade. The caspases ... The ATM protein kinase detects DNA damage and in response to this activates DNA repair factors and inhibits cell cycle ...
... with overproduction of prostaglandin E2 and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB ... In contrast to Cer, that is predominantly pro-apoptotic, Sph-1P is mainly an anti-apoptotic messenger by stimulating G-protein- ... 114] showed that Res induces apoptosis through a concurrent increase of de novo Cer and decrease of anti-apoptotic Sph-1P and ... In addition to the apoptotic potential of CAPE in cancer cells a coherent manipulation of Cer levels may improve the efficacy ...
... and is far more upstream in the apoptotic signaling cascade than Bcl-xL. Restimulation of activated primary human T cells via ... The growing subfamily of death receptors is part of the tumor necrosis factor (TNF)/nerve growth factor receptor superfamily. ... FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. ... Thus, freshly activated T cells resemble CD95 type II cells, whereas long-term activated T cells resemble type I cells. In ...
... cause inflammation with activation of extracellular matrix proteases, and impair the clearance of apoptotic cells by lung ... Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor ... Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice. J Clin Invest. 2011; ... abnormal apoptotic homeostasis (an apoptotic rate greater than the rate of clearance of dead cells by efferocytosis; ref. 51), ...
... apoptotic ATPases, proteins containing NACHT leucine-rich repeat, and proteases similar to mitochondrial HtrA-like protease, ... it requires a QS factor, which is called the extracellular death factor. The study of phenoptosis in bacteria is of great ... may be used for the development of drugs that will activate mechanisms of phenoptosis and promote the destruction of pathogenic ... KEY WORDS: bacteria, phenoptosis, programmed cell death, cell population, QS, autoinducers, extracellular death factor, ...
... mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 ... It is a pro-apoptotic protein that is activated by caspase cleavage.bcl-2-Associated X Protein: A member of the Bcl-2 protein ... The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in ... can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic ...
The apoptotic effect of TQ was much more dramatic after 12 h treatment and the activity of Caspases 3 and 9 was increased. Also ... In addition, the apoptotic process can be activated in response to stress conditions, toxic chemicals, physical agents, etc (13 ... are attributable to environmental factors (2). However, it is not an easy task to eliminate carcinogenic factors from the ... The caspase 3 and 9 colorimetric protease assay1 ApoTarget TM kit was used for the in vitro determination of proteolytic ...
Cannabinoids causes tumor cell death through apoptotic mechanisms. In one study, cannabinoids were found to have an anti- ... MMP are proteases and are increased in the presence of gliomas signaling the invasiveness of the tumor. Cannabinoid inhibition ... Another significant concept produced by the research is cannabidiol inhibition of HIF1-alpha (or hypoxia induced factor) which ... in activating apoptosis in glioma cell lines through this receptor (9). THC is a mimetic of anandamide and may induce apoptosis ...
The apoptotic phenotype is characterized by active cysteine-aspartic proteases (caspases), and the metastatic phenotype is ... Mitogen activated protein kinase. MMP:. Matrix metalloproteinases. P115RhoGEF:. Rho guanine nucleotide exchange factor-1 ... epidermal growth factor (EGF), interleukin tumor necrosis factor (IL1_TNF), transforming growth factor-beta (TGF-beta), G ... Beta-arrestin is activated by GPCRs and activates the MAPK and PI3K/AKT signaling pathways by Src activation [52, 53]. Beta- ...
... activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle ... Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate ... cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors ... After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different ...
Nuñez G., Benedict M. A., Hu Y., Inohara N. Caspases: the proteases of apoptotic pathway. Oncogene, 17: 3237-3245, 1998. ... It would seem logical that wherever estrogen is produced, the determining factor would be the amount of estrogen available to ... Initiator caspases such as caspase-9 or caspase-8 can activate the apoptotic pathway not only by activating caspase-3 but also ... the apoptotic-signaling pathway activated by aromatase inhibitors and antiestrogens is likely to be mediated via the ...
Activated protein C (APC), an endogenous vitamin K-dependent serine protease with multiple biological activities, may meet ... Tumor necrosis factor (TNF) has been suggested to be a factor in the acute renal failure in sepsis or endotoxemia. Passive ... Treating cells with SNAP in addition to DQ produced synergistic cytotoxicity that minimized differences in apoptotic cell death ... serve as substrates for the calcium-activated cysteine protease calpain.. ...
Owing to their proteolytic and apoptotic potential, lysosomal proteases must remain under tight regulatory control, and their ... However, aging is the greatest risk factor for developing AD, and the vast majority (,95%) of AD cases develop sporadically ... By directly binding Aβ, reducing plaque accumulation, and activating autophagy, cystatin C appears beneficial for AD; however, ... Lysosomal proteases play pivotal roles in regulating and executing several steps in the autophagic pathway from initial ...
... despite apoptotic caspase activation, was specific from apoptosis and as time passes allowed for secretion of comparable levels ... and Innate Immunity to CD271 mice secreted comparable amounts of tumor necrosis factor (TNF) and IL-6 upon engagement of ... Sufferers with mutations in leading to impaired protease activity screen auto-inflammation (Luksch et?al., 2013). Nevertheless ... Mitogen-Activated Protein Kinase *Mitogen-Activated Protein Kinase Kinase *Mitogen-Activated Protein Kinase-Activated Protein ...
... which may activate an apoptotic pathway. Over-expression of p75NTR and pro-NGF may be caused by oxidative stress (Su et al. ... This generally occurs when pro-NGF outcompetes a survival factor called BDNF does, in older brains where the brain cells are ... MMP-9, the protease in our circuit, degrades soluble and insoluble amyloid. ... They activate two classes of receptors - tyrosine receptor kinases (Trks), whose activation supports the neuron, and p75NTR, ...
... which is activated to initiate apoptosis (17). It is believed that procaspase activating compound-1 (PAC-1) protein is one of ... belongs to the cysteine protease family and is an important downstream effector protease of T-cell apoptosis. It is widely ... Caspase-3 can regulate the activity of many kinds of anti-apoptotic associated genes, such as (21). Apoptotic members such as ... Once considered the risk factors; modifiable risk factors, outdoor air pollution and mode of delivery (following caesarian ...
... have been considered as major factors in TSA manufacturer accelerating metastasis. MMPs are extracellular proteases and zinc- ... Pro- and anti-apoptotic Bcl-2 family interact in apoptotic procedure. Bcl-xL and Bcl-2, the anti-apoptotic protein, can ... that ARC suppresses the production of nitric oxide and inducible nitric oxide Akt1 synthase as well as p38 mitogen-activated ... Snail is usually a major EMT switch transcription factor that increases TSA manufacturer N-cadherin, -catenin, and vimentin and ...
The possible etiological factor is changing in virulence factor or the lack of protective immunity of the population ( ... The ER is also important during bacterial infection, and bacterial effectors that activate the ER stress sensors have been ... in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway ... We hypothesize that additional factors, rather than just the ability to obtain CPAP, may uniquely affect follow-up and ...
Wick W, Wild-Bode C, Frank B and Weller M: BCL-2-induced glioma cell invasiveness depends on furin-like proteases. J Neurochem ... Vo TM, Burchett R, Brun M, Monckton EA, Poon HY and Godbout R: Effects of nuclear factor I phosphorylation on calpastatin (CAST ... Ashe PC and Berry MD: Apoptotic signaling cascades. Prog Neuropsychopharmacol Biol Psychiatry. 27:199-214. 2003. View Article ... The downstream calpains were activated and dysregulated by the increased calcium levels. The mitochondrial membrane potential‑ ...
Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors. Genome ... Cellular NSM2 was activated by UV-B radiation (Fig. 3A) as well as high osmolarity (Fig. 3B; the effects of adding NaCl and ... 5B). The UV-B pellets were more abundant in protein, most likely due to the increased proportion of apoptotic bodies. The HO ... Purpose.: Since homeostasis at the ocular surface requires a delicate balance between numerous factors, and the external ...
Platelet Derived Growth Factor Receptors *Polyamine Synthase *Protease-Activated Receptors *PrP-Res ... CategoriesActivator Protein-1. Post navigation. Previous PostPrevious Secreted matrix metalloproteinases (MMP)-2 and MMP-9 and ... Open up in another window Shape 1 Inhibitory aftereffect of UA/US597 for the proliferation of human being hepatic tumor HepG2, ...
DAG binds and activates some PKCs, most important, inT cells PKCθ, a process important for activating the transcription factors ... One of the features of an apoptotic cell is the presentation of a variety ofintracellular molecules on the cell surface, such ... These neutrophil extracellular traps (NETs) comprise a web of fibers composedof chromatin and serine proteases that trap and ... and calcineurin activates NFAT,which then translocates to the nucleus. NFAT is a transcription factor, which activates the ...
For example, it is possible to model cardiac myocyte apoptosis, a process in which activated caspase-3 generates the cleaved ... Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol 2001, 3: 346- ... until proteases in the extracellular space degrade the latent peptide. In most databases, TGF-beta 1 canonical sequence ( ... corresponding to the precursor) is annotated with GO:0005160 transforming growth factor beta receptor binding. ProForm allows ...
Our previous function revealed that the experience of the mobile serine protease TMPRSS2, which activates many coronaviruses ( ... Clearance of apoptotic neutrophils Apoptotic cells could be eliminated by various types of phagocytes via efferocytosis. A ... Univariate analysis was used to select the potential prognostic factors of treatment end result. The factors having a P-value ... PRP Rabbit polyclonal to Adducin alpha are also rich in numerous active factors, such as transforming growth factor and ...
... of apoptotic nuclei. After transfection of GPC3 or GPC3ΔHS, 27-30% of the cells displayed typical apoptotic nuclear morphology ... C) Processed GPC3 activates JNK. MCF-7 cells were transfected as in A and B. Normalized cell extracts were analyzed by Western ... To identify the processing site, we mutated four potential protease-cleavage consensus sequences in GPC3. All of these ... growth factors, adhesion, and matrix molecules; and they are potentially involved in shaping the concentration gradients and ...
Activated ERK regulates growth factor-responsive targets in the cytosol and also translocates to the nucleus where it ... like and cysteine protease protein (CPP)-32-like proteases. J Exp Med 185: 601-607. [PubMed] ... This cascade can prevent cell death through Erk2 and p90 (Rsk) activation and the phosphorylation of apoptotic and cell cycle ... Lang, CH and Frost, RA (2002). Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding ...
Platelet Derived Growth Factor Receptors *Polyamine Synthase *Protease-Activated Receptors *PrP-Res ... We noticed that EGFR signaling promotes rest via mitogen-activated proteins kinase/extracellular signalCregulated kinase and ... 1 TGFa overexpression raises sleep.(A to D) ISH of and in the 5-dpf zebrafish mind (schematic) (A). A, anterior; L, lateral; V ... Scale pubs, 30 m (B, B, D, and D) and 50 m (A and C). (E to H) Carrying out a 1-hour HS (yellowish bars), pets were less ...
We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in ... Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the ... platelet-derived growth factor [31, 33], sonic hedgehog, Insulin-like growth factor, Transforming growth factor beta [34, 35], ... We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in ...
  • Expression of APAF1, caspase 9 and caspase 3 activities confirmed the intrinsic apoptotic pathway after SCI. (springer.com)
  • The apoptosome is a multimolecular holoenzyme complex assembled around the adaptor protein Apaf1 (apoptotic protease activating factor 1) upon mitochondria-mediated apoptosis which must be stimulated by some type of stress signal. (wikipedia.org)
  • The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. (biologists.org)
  • This function of Apaf1 is carried out during the cell life and is not related to its apoptotic role. (biologists.org)
  • The apoptotic protease activating factor 1 (Apaf1) is one of the most studied proapoptotic proteins. (biologists.org)
  • Cytochrome c is then released from mitochondria to activate adapter protein apoptotic protease-activating factor-1 (APAF1), which forms the apoptosome with dimerized initiator caspase 9. (biolegend.com)
  • Auf www.antikoerper-online.de finden Sie aktuell 224 Apoptotic Peptidase Activating Factor 1 (APAF1) Antikörper von 34 unterschiedlichen Herstellern. (antikoerper-online.de)
  • Clofarabine has also been shown to act directly on mitochondria by altering the transmembrane potential with release of cytochrome c, apoptotic-inducing factor (AIF), apoptosis protease-activating factor 1 (APAF1) and caspase 9 into the cytosol. (selleckchem.com)
  • Apoptosis (programmed cell death), triggers an extrinsic (death receptor-mediated signaling) or an intrinsic (mitochondria-mediated signaling) pathway to activate caspase-3, leading to morphological alterations (e.g. (spandidos-publications.com)
  • The dualistic role of the retinoic acid signaling pathway in cancer is revealed in its gene transcription targets, cross-talk with other transcription factors, mediation of apoptotic pathways, and influence in the immune system. (omicsonline.org)
  • Upon the releasing of cytochrome c from the intermembrane space of mitochondria and binding to Apaf-1 molecules, a heptameric apoptosome complex is formed and triggers the downstream cascade of caspases. (ac.ir)
  • and (5) activating cascade of caspases involving caspases 12 and 3. (mdpi.com)
  • For dying cells to adopt these features, the activation of a family of cysteine proteases, termed caspases, is required. (aspetjournals.org)
  • This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. (spandidos-publications.com)
  • These pro-apototic factors in turn activate initiator and executer caspases. (biologists.org)
  • The direct cleavage of caspases ( 2 ), disruption of nuclear-cytoplasmic trafficking ( 3 , 4 ), relocalization of proapoptotic proteins ( 5 , 6 ), and cleavage of essential apoptotic adaptor proteins ( 7 , 8 ) have all been shown to occur as a result of action of Picornavirus protease activity and together suggest mechanisms by which picornaviruses can alter host cell apoptotic death pathways. (asm.org)
  • During apoptosis, this motif is cleaved by caspases, causing the release of cytochrome c into the cytosol, which then further promotes caspase activity and, by extension, becomes pro-apoptotic. (thermofisher.com)
  • This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC.A third apoptotic caspase, DRICE, is activated throughout the length of individualizing spermatids in a process that requires the product of the driceless locus, which also participates in individualization.Our results demonstrate that multiple caspases and caspase regulators, likely acting at distinct points in time and space, are required for spermatid individualization, a nonapoptotic process. (nih.gov)
  • This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC. (nih.gov)
  • This antibody will be useful in studies of the activation of caspases through Apaf-1 and also in metastatic melanomas where Apaf-1 is inactivated which leads to defects in the execution of apoptotic cell death. (creative-biogene.com)
  • The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the main executioners of apoptosis. (ebi.ac.uk)
  • Thus, the activated caspases kill the cells by proteolysis of key cellular substrates. (aacrjournals.org)
  • They activate caspase-dependent cell death pathways by suppressing the ability of IAPs to inhibit caspases. (aacrjournals.org)
  • Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. (wikipedia.org)
  • As caspase-9 cleaves proteins, it activates other caspases from its family. (wikibooks.org)
  • This apoptosome then activates a cascade of cellular destruction events, beginning with the activation of death-execution effector caspases, such as caspase 3, followed by the activation of downstream caspases, ultimately resulting in the hallmark of apoptosis including condensation of nuclear and cytoplasmic contents, fragmentation of nuclear DNA, and membrane blebbing. (spiedigitallibrary.org)
  • Activated caspases induce apoptosis. (ersjournals.com)
  • Recruitment of procaspase-9 to the apoptosome results in its activation, allowing it to cleave and activate executioner caspases, such as caspase-3, which orchestrate the destruction of the cell ( Boatright and Salvesen, 2003 ). (rupress.org)
  • Similarly to caspase-8, active caspase-9 then proteolytically activates downstream effector caspases, which by degrading various cellular proteins propagate the apoptotic signal. (bloodjournal.org)
  • Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1-associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (rupress.org)
  • Caspases lead to the proteolysis of a number of cellular substrates, a process which finally results in the apoptotic collapse of the cell. (rupress.org)
  • Caspases are present as inactive zymogens that are activated during apoptosis ( 6 ). (aacrjournals.org)
  • Initiators such as caspase-8 and caspase-9 are apical caspases that are activated on binding to specialized molecular platforms that are assembled through selective protein-protein interactions. (aacrjournals.org)
  • Activated initiator caspases can then cleave and activate effector caspases, such as caspase-3 and caspase-7, through trans-proteolytic processing ( 12 ). (aacrjournals.org)
  • Caspases, a family of cysteine acid proteases, are central regulators of apoptosis. (cellsignal.com)
  • Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7), which in turn cleave cytoskeletal and nuclear proteins like PARP, α-fodrin, DFF and lamin A, and induce apoptosis. (cellsignal.com)
  • Fas and TNFR activate caspases 8 and 10 (2), DNA damage leads to the activation of caspase-9 and ER stress leads to the calcium-mediated activation of caspase-12 (3). (cellsignal.com)
  • [7] Both pathways induce cell death by activating caspases , which are proteases , or enzymes that degrade proteins. (wikipedia.org)
  • The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately. (wikipedia.org)
  • Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis. (wikipedia.org)
  • This process is regulated by proteases called caspases, as well as signaling proteins from the Bcl-2 family. (biolegend.com)
  • Initiator caspases are activated by dimerization, which is driven by several pathways described below. (biolegend.com)
  • Dimerized initiator caspases will cleave and activate executioner caspases. (biolegend.com)
  • Granzyme B can directly cleave and activate initiator and executioner caspases. (biolegend.com)
  • In this study, using the human T-lymphoma cell line, Jurkat cells, we investigated the apoptotic signal transduction mediated by FTY720, in particular comparing its role on the cleavage of caspases, with that mediated by etoposide or anti-Fas antibody. (aspetjournals.org)
  • Pretreatment with a broad caspase inhibitor [benzyloxycarbonyl-Val-Ala-Asp-(Ome) fluoromethyl ketone] markedly decreased the incidence of apoptotic cells induced by FTY720, etoposide, and anti-Fas antibody, through the abrogation of cleavage of Bid, poly(ADP-ribose) polymerase, and caspases 3, 8, and 9. (aspetjournals.org)
  • All caspases are synthesized as proenzymes and activated by cleavage at specific aspartate residues. (aspetjournals.org)
  • It was proposed that the "initiator" caspases with a long prodomain, such as caspases 8, 9, and 10, directly or indirectly activate the "effector" caspases, such as caspases 3, 6, and 7 ( Cohen, 1997 ). (aspetjournals.org)
  • The activated effector caspases then cleave intracellular substrates, such as poly(ADP-ribose) polymerase (PARP) and lamins, during the execution phase. (aspetjournals.org)
  • Numerous studies have implicated a variety of intracellular signaling pathways, including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and Jak/signal transducers and activators of transcription, as effectors of these extracellular trophic factors. (aspetjournals.org)
  • Binding of growth factors to their respective receptors results in the activation of individual and combined pathways resulting in pleiotropic effects on cellular biochemistry. (aspetjournals.org)
  • Despite a wide array of distinct trophic factors and receptors that govern the survival of specific cells, many of these receptors use common intracellular signaling molecules and pathways to mediate their signals. (aspetjournals.org)
  • Three pathways that have taken center stage in survival signaling are the phosphatidylinositol 3-kinase (PI3K)/Akt, the Ras/mitogen-activated protein kinase, and the Jak/signal transducers and activators of transcription (STAT) pathways. (aspetjournals.org)
  • These pathways have been shown to mediate survival signals in several cell types and model organisms and in response to a diverse array of growth factors. (aspetjournals.org)
  • This review will present an overview of our current understanding of programmed cell death, also referred to as apoptosis, focusing on growth factor signaling pathways in the context of cell survival and the role of these pathways in carcinogenesis. (aspetjournals.org)
  • How is activation of mitochondria-based pathways for the signaling of apoptotic and necrotic cell death avoided under conditions of hypoxia, anoxia, diapause, estivation and anhydrobiosis? (biologists.org)
  • Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions. (wikipedia.org)
  • The depletion of anticoagulant and anti-inflammatory proteins, in particular, protein C and its co-factor, protein S, may also promote thrombus formation, inhibit fibrinolysis and lead to further activation of the inflammatory pathways. (wikipedia.org)
  • Picornavirus proteases also cleave nucleoporins, disrupting the orchestrated manner in which signaling pathways use active nucleocytoplasmic trafficking, including those involved in apoptosis. (asm.org)
  • Picornaviruses can selectively alter cellular pathways in order to promote viral replication, mostly through the action of viral proteases, including modulation of proapoptotic factors or processes. (asm.org)
  • In this minireview, we aim to review and discuss current literature on Picornavirus modulation of cell death pathways with a view to integrating diverse studies to form a rational informed model of Picornavirus disruption of apoptotic pathways. (asm.org)
  • The extrinsic and intrinsic apoptosis pathways converge to cleave and activate procaspase-3 to derive caspase 3, which is termed an executioner caspase. (asm.org)
  • While several signaling pathways have been suggested to play a role in cytokine-mediated cell death ( 1 ), it remains unclear how these pathways cooperate to induce apoptosis in β-cells. (diabetesjournals.org)
  • Here we report characterization of apoptotic signaling pathways activated by NO · in these cells by cDNA microarray expression and immunoblotting. (aacrjournals.org)
  • NO · also modulated levels of several gene products in the mitochondria-dependent and death-receptor-mediated apoptotic pathways. (aacrjournals.org)
  • Collectively, these data show that NO · exposure activated a complex network of responses leading to p53-dependent apoptosis via both mitochondrial and Fas receptor pathways, which were abrogated in the presence of mutant p53. (aacrjournals.org)
  • The caspase cascade can be activated by different pathways (fig. 1 ⇓ ) 5 . (ersjournals.com)
  • Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. (thefreelibrary.com)
  • Apoptotic pathways of cell death. (cdc.gov)
  • Direct DNA damage by ionizing radiation or UV can activates the interconnected apoptotic pathways by stimulation of protein kinases from phosphoinositide-3-kinases family. (bio-rad.com)
  • These stimulated kinases directly or indirectly activate phosphorylation of proteins from apoptotic pathways: tumor suppressor p53 , breast and ovarian cancer susceptibility protein 1 ( Brca1 ), E2F transcription factor 1 ( E2F1 ), proto-oncogene tyrosine-protein kinase c-Abl and cell cycle regulator RAD9 . (bio-rad.com)
  • Activated c-Alb participates in apoptotic pathways (e.g. via phosphorylation tumor p53-related protein ( p73 ) [ 8 ], transcription factor c-Jun or apoptosis-related cysteine protease 9 ( Caspase-9 ). (bio-rad.com)
  • E2F may activate apoptosis pathways by stimulation of p53 14-3-3 protein, type tau ( 14-3-3 tau ) is required for expression and induction of E2F1 apoptotic targets, such as p73 , Apaf-1 , and apoptosis-related cysteine protease 3 ( Caspase-3 ). (bio-rad.com)
  • Stimulation of apoptosis is responsible for the elimination of potentially harmful or premalignant cells, whereas suppression of apoptotic pathways can lead to uncontrolled cell proliferation and formation of malignancies. (rsc.org)
  • The induction of apoptotic pathways in cancer cells offers a novel and potentially useful approach to improve patient responses to conventional chemotherapy. (aacrjournals.org)
  • Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. (aacrjournals.org)
  • However, little is known about the role of TFPI-2 in the induction of apoptotic pathways in glioblastomas. (aacrjournals.org)
  • It has dual functions at the molecular level: Lipin 1 serves as a transcriptional coactivator in liver, and a phosphatidate phosphatase in triglyceride and phospholipid biosynthesis pathways (5). (cellsignal.com)
  • Lipin 1 is regulated by mTOR, illustrating a connection between adipocyte development and nutrient-sensing pathways (6). (cellsignal.com)
  • By undergoing fission they generate fragmented discrete mitochondria, a process which is regulated by the mitochondrial fission proteins, dynamic-related peptide-1 (Drp1), human fission protein-1 (hFis1), mitochondrial fission factor (Mff) and mitochondrial dynamics proteins 49 and 51 (MiD49 and 51). (springer.com)
  • Plant NB-LRR proteins belong to the STAND (signal transduction ATPases with numerous domains) superfamily, which includes the animal apoptotic proteins Apaf-1/CED4 and innate immune receptors of the nucleotide-binding domain and leucine-rich repeat-containing proteins (NLR) family ( 5 ). (pnas.org)
  • STAND proteins are molecular switches that toggle from an ADP-bound "off" position to an ATP-bound "on" state that activates downstream signaling. (pnas.org)
  • Receptor engagement then leads to the recruitment of death domain (DD) containing proteins as the Fas-associated DD, which serve to bind and activate caspase-8 that in turn ultimately initiates a cascade of caspase activation (Fig. 1 ). (aspetjournals.org)
  • Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). (spandidos-publications.com)
  • During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. (wikipedia.org)
  • These proteases are essential for viral polyprotein processing and also cleave cellular proteins. (asm.org)
  • Picornavirus proteases cleave proapoptotic adaptor proteins, resulting in downregulation of apoptosis. (asm.org)
  • The single open reading frame of the genome is translated into a large polyprotein that undergoes posttranslational processing ( cis and trans cleavage) by the virally encoded proteases to yield mature, structural or nonstructural proteins ( 14 ). (asm.org)
  • The viral proteases not only participate in the maturation of the viral proteins but also act against cellular factors, resulting in host cell shutoff and increased virus replication. (asm.org)
  • Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two proapoptotic Bcl-2 proteins, Bad and Bax, were examined in β-cells. (diabetesjournals.org)
  • Multidomain proapoptotic proteins, such as Bax and Bak, contain the conserved Bcl-2 homology (BH) domains 1-3. (diabetesjournals.org)
  • Many apoptotic cell deaths in Drosophila utilize the REAPER/HID/GRIM family proapoptotic proteins. (nih.gov)
  • These proteins promote cell death, at least in part, by disrupting interactions between the caspase inhibitor DIAP1 and the apical caspase DRONC, which is continually activated in many viable cells through interactions with ARK, the Drosophila homolog of the mammalian death-activating adaptor APAF-1. (nih.gov)
  • Inhibitors of apoptosis proteins X-chromosome-linked inhibitor of apoptosis, cellular inhibitor of apoptosis protein-1, and survivin were significantly down-regulated in TK6 cells, but not in WTK1 cells. (aacrjournals.org)
  • Proteins containing this domain include the low affinity neurotrophin receptor p73, Fas, FADD (Fas-associated death domain protein), TNF-1 (tumour necrosis factor receptor-1), Pelle protein kinase, and the Tube adaptor protein [ PMID: 15226512 ]. (ebi.ac.uk)
  • Proteins containing CARD include Raidd, APAF-1 (apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation). (ebi.ac.uk)
  • Mechanisms that may contribute to lower satellite cell proliferation and differentiation in muscles of the OZR could include decreases in the expression levels of myogenic regulatory factor proteins. (physiology.org)
  • Activated neutrophils release extracellular traps (neutrophil extracellular traps, NETs), an extracellular matrix composed of nuclear and mitochondrial DNA armed with granular proteins, cell-specific proteases, and antimicrobial peptides ( 10 , 11 ). (pnas.org)
  • Caspase-9 is a protease that cleaves proteins. (wikibooks.org)
  • We found that ADEVs released in response to IL-1β (ADEV-IL-1β) and TNFα (ADEV-TNFα) were enriched with miRNAs that target proteins involved in neurotrophin signaling. (nature.com)
  • In this Review, we discuss how a pro-apoptotic subgroup of the BCL2 protein family, known as the BH3-only proteins, controls apoptosis and anoikis during mammary gland homeostasis and to what extent their inhibition confers tumor suppressive functions in metastatic breast cancer. (biologists.org)
  • Specifically, the role of the two pro-apoptotic BH3-only proteins BCL2-modifying factor (BMF) and BCL2-interacting mediator of cell death (BIM) will be discussed here. (biologists.org)
  • We assess current developments in treatment that focus on mimicking the function of the BH3-only proteins to induce apoptosis, and consider their applicability to restore normal apoptotic responses in anchorage-independent disseminating tumor cells. (biologists.org)
  • 6 ] Moreover, JNK stimulates activity of proapoptotic proteins, Bcl-2 modifying factor ( BMF ) and BCL2-like 11 factor ( Bim ). (bio-rad.com)
  • Other proteins released from the intermembrane space of mitochondria are the Apoptosis Inducing Factor (AIF), Smac/Diablo and Omi. (rsc.org)
  • Members of the Bcl-2 family are pivotal regulators of the apoptotic process ( Antonsson and Martinou, 2000 ) and include both proteins that promote cell survival (e.g. (jneurosci.org)
  • The effects of [beta]-sitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. (thefreelibrary.com)
  • Structural, Biochemical and Functional Analyses of CED-9 Recognition by the Pro-apoptotic Proteins EGL-1 and CED-4. (tsinghua.edu.cn)
  • Myeloid cell leukemia type 1 (Mcl-1) is one of the antiapoptotic Bcl-2 family proteins. (intechopen.com)
  • These movements result from competitive microtubule polymerization and depolymerization or through the actions of microtubule motor proteins (1). (cellsignal.com)
  • To reach their native conformation, many secretory proteins require the formation of intra- or inter-molecular disulfide bonds (1). (cellsignal.com)
  • The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. (aacrjournals.org)
  • The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. (aacrjournals.org)
  • Background: Caspase-3 (CPP-32, Apoptain, Yama, SCA-1) is a critical executioner of apoptosis, as it is either partially or totally responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (1). (cellsignal.com)
  • Binding of a ligand to its respective receptor activates adaptor proteins that contain death domains, such as FADD and TRADD. (biolegend.com)
  • The apoptotic protease-activating factor 1 (Apaf-1) receives the death signal in the intrinsic or mitochondrial pathway of apoptosis. (ac.ir)
  • The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced β-cell death is unclear. (diabetesjournals.org)
  • CONCLUSIONS Our findings demonstrate that the intrinsic mitochondrial apoptotic pathway contributes significantly to cytokine-induced β-cell death and suggest a functional role of calcineurin-mediated Bad Ser136 dephosphorylation and Bax activity in cytokine-induced apoptosis. (diabetesjournals.org)
  • Signals activating the "intrinsic apoptotic pathway" converge on the mitochondria, leading to mitochondrial membrane permeabilization and subsequent release of cytochrome c from the intermembranous space ( 3 ). (diabetesjournals.org)
  • In the intrinsic pathway, several adverse factors act upon mitochondria to cause loss of the mitochondrial membrane potential, resulting in leakage into the cytosol of cytochrome C (Cyto C), which together with apoptotic protease activating factor 1 forms the apoptosome that activates caspase-9. (cdc.gov)
  • The two molecular programs are known as the extrinsic pathway operating downstream of death receptors, such as Fas and the tumor necrosis factor receptor family, and the intrinsic pathway, which is activated by a diverse array of stress signals. (aacrjournals.org)
  • The identification of cytochrome c as an apoptogenic factor released from mitochondria marked a pivotal breakthrough in uncovering the importance of this organelle in the intrinsic pathway of apoptosis ( 3 ). (aacrjournals.org)
  • Weak external signals may also activate the intrinsic pathway of apoptosis. (wikipedia.org)
  • The intrinsic pathway is triggered by detection of cellular stresses, such as DNA damage and hypoxia, or by the absence of signaling from growth factors, hormones, and cytokines. (biolegend.com)
  • Granzyme B can also cleave Bid to induce cytochrome c release and the intrinsic apoptotic pathway. (biolegend.com)
  • Upregulation of cleaved caspase 3,7 were detected by western blot in addition to Apaf-1 and caspase 9 expressions argues that cell death takes place via the intrinsic apoptotic pathway in which release of cytochrome c from the mitochondria triggers the assembly of a caspase activation complex. (blogspot.com)
  • The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. (nih.gov)
  • Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. (nih.gov)
  • Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the caspase-recruitment domain (CARD) of Apaf-1 and through inhibition of apoptosome formation. (nih.gov)
  • In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). (rcsb.org)
  • On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. (rcsb.org)
  • Cytochrome c/Apaf-1/caspase-9 form a socalled apoptosome, amplifying the caspase cascade. (biovendor.com)
  • We found that the cytochrome c /apoptotic protease-activating factor-1 (apoptosome)-dependent caspase activation is deficient in human non-small cell lung cancer (NSCLC) NCI-H460 cells. (aacrjournals.org)
  • This dysfunctional apoptosome activity was not correlated with any decrease of apoptosome component factors, but it was linked to an increased X-linked inhibitor of apoptosis protein (XIAP). (aacrjournals.org)
  • The liberated cytochrome c , along with adenine nucleotides, initiates formation of an apoptosome consisting of Apaf-1 3 oligomers. (aacrjournals.org)
  • In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of an apoptosome. (wikipedia.org)
  • An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. (wikipedia.org)
  • The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic transmission electron microscopy in 2002, revealing a heptameric wheel-like particle with 7-fold symmetry. (wikipedia.org)
  • Recently, a medium resolution (9.5 Ångström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. (wikipedia.org)
  • Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. (wikipedia.org)
  • The stable APAF-1 and cytochrome mutimeric complex fit this description, and is now called the apoptosome. (wikipedia.org)
  • There are hidden routes for cell death as well, which are independent of APAF-1 and therefore the apoptosome. (wikipedia.org)
  • The wheel-shaped heptameric complex with sevenfold symmetry structure of the apoptosome was first revealed at 27 Å resolution by electron cryomicroscopy techniques and has a calculated mass of about 1 MDa (Acehan et al. (wikipedia.org)
  • Released cytochrome c interacts with apoptotic protease-activating factor 1, ATP, and pro-caspase 9 to form the apoptosome. (spiedigitallibrary.org)
  • Once in the cytosol, cytochrome c binds to Apaf-1 to form the apoptosome complex. (rupress.org)
  • It is the core of the apoptosome, which is formed upon triggering of the mitochondrial apoptotic pathway. (biologists.org)
  • The complex of procaspase-9, cytochrome c, and Apaf-1 is known as the apoptosome. (bloodjournal.org)
  • Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. (abcam.com)
  • Activated caspase 9 primary signaling occurs through caspase 3, which it cleaves and activates. (novusbio.com)
  • During the assay, activated caspase-3 cleaves this substrate between DEVD and AMC, generating highly fluorescent AMC that can be detected using a fluorescence reader with excitation at 380 nm and emission between 420 - 460 nm. (cellsignal.com)
  • 4. The method of claim 1, wherein said polarized scorpion venom solution prevents cancer and tumor growth. (freepatentsonline.com)
  • RESEARCH DESIGN AND METHODS Human and rat islets and INS-1 cells were exposed to a combination of proinflammatory cytokines (interleukin-1β, interferon-γ, and/or tumor necrosis factor-α). (diabetesjournals.org)
  • Proinflammatory cytokines, particularly interleukin (IL)-1β in combination with interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α, have been implicated in the elimination of β-cells in type 1 diabetes ( 1 ). (diabetesjournals.org)
  • CAAs provide fuel, growth factors, and cytokines and transdifferentiate into other stromal cells to alter tumor growth, metastasis, and drug responses. (jci.org)
  • 4 One involves the ligation of death receptors, such as CD95 and tumor necrosis factor-receptor (TNF-R1), which on binding of the adapter protein FADD, recruit procaspase-8 into the death-inducing signaling complex. (bloodjournal.org)
  • The extrinsic pathway is mediated by a variety of death receptor ligands, including tumor necrosis factor (TNF) and Fas ligand (FaSL), that trigger apoptosis by binding to cell surface receptors. (cdc.gov)
  • Semiquantitative reverse transcription-PCR depicted increased expression of tumor necrosis factor-α and Fas ligand and the related death domains tumor necrosis factor receptor 1-associated death domain and Fas-associated death domain. (aacrjournals.org)
  • It was found that a dihydroxylated water-soluble sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414). (aacrjournals.org)
  • The extrinsic pathway is regulated by signaling through receptors of the Tumor Necrosis Factor receptor (TNFR) superfamily. (biolegend.com)
  • It is also becoming clear that mitosis and apoptosis are toggled or linked in some way and that the balance achieved depends on signals received from appropriate growth or survival factors. (wikipedia.org)
  • Chemotherapeutic agents, UV irradiation, and other agents induce caspase activation mainly via the mitochondrial pathway, which involves mitochondrial integration of apoptotic signals and subsequent release of cytochrome c into the cytosol. (aacrjournals.org)
  • The extrinsic pathway of apoptosis is triggered by external signals that activate cell surface death receptors, including Fas. (thefreelibrary.com)
  • Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. (nih.gov)
  • caspase-9 thus is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (biovendor.com)
  • Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. (nih.gov)
  • Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (nih.gov)
  • Animal PCD is primarily achieved by the activation of the Asp-specific Cys protease (caspase) cascade ( Bratton and Cohen, 2001 ). (plantphysiol.org)
  • Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. (bloodjournal.org)
  • 9 10 Second, caspase-9 can activate procaspase-8 via the caspase-3 and caspase-6 cascade, thus amplifying the receptor-derived signal and via Bid cleavage also the mitochondrial pathway. (bloodjournal.org)
  • An etoposide -treated DU145 prostate cancer cell exploding into a cascade of apoptotic bodies. (wikipedia.org)
  • Vaccine exposure was accompanied by significant increases in the levels of activated caspase 3, a key effector caspase in the apoptosis cascade. (blogspot.com)
  • Once in the cytosol, cytochrome c complexes with apoptosis-protease activating factor-1, which, in the presence of ATP, leads to activation of the initiator caspase, caspase-9. (diabetesjournals.org)
  • Cyt c in the cytosol catalyzes the oligomerization of apoptotic protease activating factor-1. (plantphysiol.org)
  • Once in the cytosol, cytochrome c interacts with its adaptor molecule, Apaf-1, resulting in the recruitment, processing and activation of pro-caspase-9. (rsc.org)
  • DNA damage-induced, p53-activated neuronal cell death has already been identified in several neurodegenerative diseases. (springer.com)
  • Animal NLRs are activated by MAMPs and by modified-self molecules in the form of danger-associated molecular patterns ( 6 ) and regulate inflammasome activation, autophagy, and cell death ( 7 ). (pnas.org)
  • In fact, the availability of growth factors is thought to define the size of various tissues by dictating the delicate balance between proliferation and cell death within a particular organ ( Conlon and Raff, 1999 ). (aspetjournals.org)
  • In fact, perturbations in cell metabolism, growth factor availability, and genotoxic agents, which result in the loss of mitochondrial function, can induce cell death even in the absence of caspase activation. (aspetjournals.org)
  • Therefore, cell death can be categorized based on the method of initiation: 1) that which is initiated from cell surface death receptor engagement or 2) death arising from mitochondrial dysfunction. (aspetjournals.org)
  • As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. (spandidos-publications.com)
  • Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death. (spandidos-publications.com)
  • Some animals like embryos of the brine shrimp, Artemia franciscana , exhibit profound metabolic depression and survive anoxia at room temperature for years ( Clegg, 1997 ) with no evidence of apoptotic or necrotic cell death. (biologists.org)
  • It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is blocked by endogenous or exogenous factors such as viruses or mutations. (wikipedia.org)
  • Apoptosis is an energy-dependent process in which dying cells activate a genetically encoded cell-death program. (diabetesjournals.org)
  • Here we used CRISPR-Cas9 mutagenesis to show that phagocyte intoxication involves uptake of dAdo via the human equilibrative nucleoside transporter 1, dAdo conversion to dAMP by deoxycytidine kinase and adenosine kinase, and signaling via subsequent dATP formation to activate caspase-3-induced cell death. (pnas.org)
  • Apoptosis was studied in roundworms and in the final stages of its cell death, there discovery of the death-inducing protease CED-3 activation became the cause of the apoptosis. (wikibooks.org)
  • Mammary gland development goes through different stages that depend on proper regulation of proliferation and programmed cell death (apoptosis) ( Fig. 1 A). Sex hormone-dependent cyclic organization of growth and survival provides the plasticity of the mammary gland that is needed for its function. (biologists.org)
  • 1 Apoptosis, also known as programmed cell death, is the form of cell elimination commonly occurring during development as well as in many physiologic and pathologic processes. (bloodjournal.org)
  • Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. (novusbio.com)
  • Neuronal cell death appears to occur through competition for trophic factors derived from target tissues, which may serve to select the proper set of neuronal connections ( Oppenheim, 1991 ). (jneurosci.org)
  • 1. Programmed cell death is as needed for proper development as mitosis is. (biology-pages.info)
  • 2004). These factors ultimately activate the effector protease, caspase-3, driving programmed cell death (Dragovich et al. (thefreelibrary.com)
  • The nature of cell death was apoptotic, as determined by annexin and DNA nick labeling. (aacrjournals.org)
  • 2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol hydrochloride (FTY720), a synthetic product derived from a metabolite of Isaria sinclairii , has been demonstrated to have a potent immunosuppressive activity that induces apoptotic cell death in T cells and several other cell lines. (aspetjournals.org)
  • Clofarabine (10 μM) combined with 4-hydroperoxycyclophosphamide (4-HC) produces more than additive apoptotic cell death than the sum of each alone. (selleckchem.com)
  • Since activation by Akt phosphorylation plays a central role in a variety of oncogenic processes, including cell proliferation, anti-apoptotic cell death, angiogenesis and metastasis, we also investigated alterations in Akt phosphorylation induced by α-mangostin treatment both in vitro and in vivo . (biomedcentral.com)
  • This cysteine protease family consists of more than 10 related members characterized by almost absolute specificity for aspartic acid in the P1 position. (biovendor.com)
  • AIF and the serine protease Omi catalyze caspase-independent downstream events in the apoptotic process. (rsc.org)
  • In addition, 20 µM luteolin had a significant inhibitory effect on multi-heavy metal mixture-induced cleavage of caspase-9, caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein. (spandidos-publications.com)
  • Through proteolytic cleavage, caspase-9 activates the effector caspase, caspase-3, leading to cleavage of numerous cellular targets and resulting in the systematic dismantling of the cell ( 4 ). (diabetesjournals.org)
  • Apoptotic cells undergo various morphological changes, including cell shrinkage, membrane blebbing, cleavage of chromosomal DNA and the release of the membrane-bound apoptotic bodies. (ersjournals.com)
  • These proteases are synthesized as inactive proenzymes which, upon proteolytic cleavage at aspartate residues, form an active complex composed of two heterodimeric subunits. (rupress.org)
  • Extrinsic pathway signaling can also cross-activate mitochondrial release of cytochrome c through caspase 8-mediated cleavage of Bid , a pro-apoptotic member of the Bcl-2 family. (biolegend.com)
  • The interaction between Hsp70 and Apaf-1 prevents oligomerization of Apaf-1 and association of Apaf-1 with procaspase-9. (nih.gov)
  • Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the WD-40 repeat region. (nih.gov)
  • The oligomerization of Apaf-1 appears to be accompanied by synchronized recruitment of procaspase-9 to the CARD motif at the Apaf-1 N-terminus. (wikipedia.org)
  • 7 8 Activated Bid triggers a conformational change of another proapoptotic molecule, Bax, which leads to its oligomerization and subsequent insertion into the outer mitochondrial membrane and finally to cytochrome c release. (bloodjournal.org)
  • How the apoptotic pathway is restricted in mature neurons and how these restrictions are overcome after pathological stimuli is unclear. (rupress.org)
  • Another pathway that is triggered by a number of apoptotic stimuli such as anticancer drugs or irradiation is essentially controlled at the mitochondrion. (bloodjournal.org)
  • The intracellular calcium produces an avalanche of reactive oxygen species (ROS), leading to mitochondria-mediated apoptotic process, in particular, during such a pathological condition [ 5 , 6 , 7 ]. (mdpi.com)
  • Cellular conditions experienced during energy-limited states - elevated calcium, shifts in cellular adenylate status, compromised mitochondrial membrane potential - are precisely those that trigger, at least in mammals, the mitochondrion to initiate opening of the permeability transition pore, to assemble additional protein release channels, and to release pro-apoptotic factors. (biologists.org)
  • As such, control or modulation of apoptotic processes is favorable to picornaviruses, and this minireview will specifically focus on the modifications of cellular processes by picornaviruses that lead to downregulation of apoptosis. (asm.org)
  • Apoptotic cells do not release their cellular contents and are quickly engulfed by phagocytic cells, and therefore avoid triggering unnecessary inflammatory responses. (biolegend.com)
  • Mitochondria produce the energy needed for normal cellular function and metabolic homeostasis by oxidative phosphorylation, 1 a process conducted by a series of five enzyme complexes located on the inner mitochondrial membrane ( fig. 1 ). (asahq.org)
  • A critical regulator of autophagy induction is the kinase mTOR, which when activated, suppresses autophagy and when not activated promotes it. (wikipedia.org)
  • Three related serine/threonine kinases, UNC-51-like kinase -1, -2, and -3 (ULK1, ULK2, UKL3), which play a similar role as the yeast Atg1, act downstream of the mTOR complex. (wikipedia.org)
  • b) For GI/S cell cycle arrest, the p53-mediated pathway through p21 is involved, as well as the pRb gene-mediated pathway, c) Alteration of cyclin G1 and Wee-1 kinase genes may be related to the G2/M arrest induced by benzene exposure, d) DNA repair genes such as Rad50 and Rad51 are markedly downregulated in p53-KO mice. (thefreelibrary.com)
  • The receptor for activated protein kinase C promotes cell growth, invasion and migration in cervical cancer. (amedeo.com)
  • JNK and p38 alpha activate transcription of c-Jun , which, in turn, excites transcription of cyclin-dependent kinase 1 ( CDK1 ). (bio-rad.com)
  • In addition, c-Alb activates protein kinase C, delta ( PKC delta ). (bio-rad.com)
  • We observed that Aβ rapidly activates c-Jun N-terminal kinase (JNK). (jneurosci.org)
  • Both PCI-2000 and PCI-2010, a tetrahydroxy bis-carbamate derivative of PCI-2000, result in increased levels of phosphorylated p38 mitogen-activated protein kinase. (aacrjournals.org)
  • Inhibition of p38 mitogen-activated protein kinase phosphorylation resulted in a synergistic increase of PCI-2000 cytotoxicity. (aacrjournals.org)
  • Treatment with this sapphyrin or PCI-2010, a congeneric tetrahydroxy bis-carbamate derivative, resulted in enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK), a stress-responsive protein kinase that participates in the regulation of apoptosis. (aacrjournals.org)
  • We report that hepatitis B vaccine exposure resulted in significant upregulation of the key genes encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil containing protein kinase 1 (ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1). (blogspot.com)
  • We confirmed that miR-125a-5p and miR-16-5p (both enriched in ADEV-IL-1β and ADEV-TNFα) targeted NTKR3 and its downstream effector Bcl2. (nature.com)
  • Activated p53 and Bax mitochondrial translocation were detected in injured spinal neurons. (springer.com)
  • By E2F and p53/TP53 in apoptotic neurons. (mybiosource.com)
  • We show that as neurons mature, cytochrome c - mediated apoptosis progresses from inhibitor of apoptosis protein-dependent to -independent regulation because of a complete loss of Apaf-1 expression. (rupress.org)
  • However, after DNA damage, mature neurons resynthesize Apaf-1 through the cell cycle-related E2F1 pathway and restore their apoptotic potential. (rupress.org)
  • Surprisingly, we find that E2F1 is sufficient to induce Apaf-1 expression in developing but not mature neurons. (rupress.org)
  • Rather, Apaf-1 up-regulation in mature neurons requires both chromatin derepression and E2F1 transcriptional activity. (rupress.org)
  • This differential capacity of E2F1 to induce Apaf-1 transcription is because of the association of the Apaf-1 promoter with active chromatin in developing neurons and repressed chromatin in mature neurons. (rupress.org)
  • These data specifically illustrate how the apoptotic pathway in mature neurons becomes increasingly restricted by a novel mechanism involving the regulation of chromatin structure. (rupress.org)
  • Importantly, we identify chromatin modification as important mechanisms by which apoptotic resistance is regulated in maturing neurons. (rupress.org)
  • Surprisingly, XIAP-deficient mature P28 neurons remained completely resistant to injection of cytochrome c ( Fig. 1 a ). (rupress.org)
  • These results indicate that the apoptotic pathway in mature P28 neurons becomes further restricted by mechanisms independent of IAPs. (rupress.org)
  • The survival of neurons is maintained primarily by neurotrophic factors that suppress the apoptotic program. (jneurosci.org)
  • Here, we show that DP5/Harakiri, a Bcl-2 homology domain 3-only member of the Bcl-2 family, is induced in motoneurons after transection of the hypoglossal nerve in mice and in sympathetic neurons after nerve growth factor (NGF) withdrawal. (jneurosci.org)
  • The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. (bloodjournal.org)
  • It has been shown that the expression of Mcl-1 in CLL is significantly associated with a failure to achieve complete remission following cytotoxic therapy, so regulation of Mcl-1 expression by coumarins could be one of the mechanisms of CLL chemotherapy. (intechopen.com)
  • In this chapter, the cytotoxic activity of coumarins and their role in Mcl-1 regulation are discussed. (intechopen.com)
  • Genes enriched in committed progenitors were mostly associated with haematopoietic differentiation, immune regulation, and metabolism 1 . (medsci.org)
  • The report 'Proprotein Convertase SubtilisinKexin Type 9 - Pipeline Review, H1 2018' outlays comprehensive information on the Proprotein Convertase Subtilisin/Kexin Type 9 (Proprotein Convertase 9 or Neural Apoptosis Regulated Convertase 1 or Subtilisin/Kexin Like Protease PC9 or PCSK9 or EC 3.4.21. (researchandmarkets.com)
  • The latest report Caspase 9 - Pipeline Review, H2 2018, outlays comprehensive information on the Caspase 9 (Apoptotic Protease Mch 6 or Apoptotic Protease Activating Factor 3 or ICE Like Apoptotic Protease 6 or CASP9 or EC targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (grandresearchstore.com)
  • Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1) . (wikipedia.org)
  • A stress stimulus can trigger the release of cytochrome c into the cytoplasm which will then bind to the C-terminus of Apaf-1 within a region containing multiple WD-40 repeats. (wikipedia.org)
  • First, the BH3-only Bax-interacting protein Bid, which is a substrate of caspase-8, becomes activated in the death receptor-mediated pathway and induces the release of cytochrome c from mitochondria. (bloodjournal.org)
  • Autocrine expression of the epidermal growth factor receptor ligand heparin-binding EGF-like growth factor in cervical cancer. (amedeo.com)
  • Retinoids are thus ideal candidates for medical therapies, as the uptake of RA (and its closely related synthetic analogues) does not require a cell surface receptor [ 1 ]. (omicsonline.org)
  • an inhibitor of IAPs) was unable to induce apoptosis ( Fig. 1 a ). (rupress.org)
  • Supravieţuirea generală la pa- caspaza 9, legată de APAF-1 (apoptotic nelor mitocondriale, a citocromului c şi a cienţii cu recedivă tumorală este sem- protease activating factor 1), formează factorului ce induce apoptoza (AIF - apop- nificativ mai scurtă la cei cu densitate cu citocromul c un complex proteic, tosis inducing factor). (yudu.com)
  • apoptotice (Apof-1) şi induce activarea o citochină multifuncţională al cărui calea extrinsecă este legată de exis- caspazei 9 (Apof-3), care iniţiază cascada nivel este corelat cu stadiul tumoral tenţa receptorilor celulari de suprafaţă, caspazelor. (yudu.com)
  • Rats CLC NumberR2-03 Document CodeA Our previous studies have proved that preventively used moxibustion could induce high expression of HSP70 in gastric mucosa in rats with stress gastric ulcer, to inhibit cell apoptosis and protect gastric mucosa [1, 2]. (scribd.com)
  • During the development process for Alzheimer's disease (AD), excessive activated extracellular glutamate receptors prompt changes in ion channels and signaling systems [ 5 , 6 , 7 ]. (mdpi.com)
  • In the first tier, extracellular pattern recognition receptors (PRRs) bind conserved microbial-associated molecular pattern (MAMP) ligands, activating a complex host response that results in MAMP-triggered immunity (MTI). (pnas.org)
  • In the second tier, plant intracellular immune receptors of the nucleotide-binding leucine-rich repeat (NB-LRR) protein family can be activated either by direct binding of effectors or, alternatively, by effector action on an associated target protein that generates a "modified-self" molecule ( 1 , 2 ). (pnas.org)
  • The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions [ PMID: 11828422 , PMID: 12655292 ]. (ebi.ac.uk)
  • Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. (rupress.org)
  • Other pro-apoptotic factors such as Smac (second mitochondria-derived activator of caspase)/DIABLO (direct inhibitor of apoptosis protein-binding protein with low pI), apoptosis-inducing factor and endonuclease G are also released from the mitochondria 8 . (ersjournals.com)
  • Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells. (aacrjournals.org)
  • Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type proteinase inhibitor that acts against a wide range of serine proteases through their nonproductive interaction with a P 1 residue in its first Kunitz-type domain ( 4 ). (aacrjournals.org)
  • It supports the neuroprotective action of activated protein C ( 10 ) and circulates in plasma as both free and in complex with C4b-binding protein (C4BP), which is an inhibitor of the classic complement pathway ( 11 ). (diabetesjournals.org)
  • In addition to viral proteases, the transmembrane 2B protein alters intracellular ion signaling, which may also modulate apoptosis. (asm.org)
  • [1] Clofarabine (10 μM) inhibits the repair initiated by 4-hydroperoxycyclophosphamide (4-HC), with inhibition peaking at the intracellular concentrations of 5 μM in chronic lymphocytic leukemia (CLL) lymphocytes. (selleckchem.com)
  • Whereas histone acetyltransferase catalyzes the acetylation of histones and relaxes chromatin to increase the accessibility of transcription factors to the promoters of the target genes, HDACs remove the acetyl groups from histones and repress transcription [ 4 ]. (hindawi.com)
  • Myogenic regulatory factors are muscle-specific helix-loop-helix transcription factors that regulate muscle-specific genes ( 12 , 25 ). (physiology.org)
  • Activated p53 regulates transcription of apoptosis regulator Bax [ 16 ], apoptotic protease activating factor ( Apaf-1 ) [ 17 ] and Bcl-2 . (bio-rad.com)
  • Human DNMT1 Primer Pair 1 for RT-PCR (reverse transcription followed by polymerase chain reaction) analysis of mRNA expression. (cusabio.com)
  • It has also been shown that the nucleotide dATP as third component binds to apaf-1, however its exact role is still debated. (wikipedia.org)
  • A JC-1 staining assay indicated that 20 µM luteolin inhibited the mitochondrial membrane potential-reducing effect of the multi-heavy metal mixture. (spandidos-publications.com)
  • Therefore, permeabilization of the outer mitochondrial membrane (OMM) is considered a crucial event during the early phase of the apoptotic process. (rsc.org)
  • This results in the increased permeability of the mitochondrial membrane, which is regulated by pro- and anti-apoptotic members of the Bcl-2 family (e.g. (biolegend.com)
  • Here, for the first time we present spontaneous mutations and recombinations of the Apaf-1 gene and its neighbouring sequences. (ac.ir)
  • Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ultraviolet irradiation resistance-associated gene (UVRAG), is required for the induction of autophagy. (wikipedia.org)
  • Still, neither the single-gene approach nor gene expression profiling alone has been shown to accurately reflect the complex network of responses that characterizes an apoptotic program. (aacrjournals.org)
  • This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (creative-biogene.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC - Caspase-7 (CASP7) is a human protein encoded by the CASP7 gene. (researchandmarkets.com)
  • On the basis of the results of large-scale gene expression studies, we conclude the following: a) Benzene induces DNA damage in cells at any phase of the cell cycle through myeloperoxidase and in the redox cycle, resulting in p53 expression through Raf-1 and cyclin D-interacting myb-like protein 1. (thefreelibrary.com)
  • The abnormal development of adipose tissues caused by mutations in the lipin 1 gene results in lipodystrophy, a condition associated with low body fat, fatty liver, hypertriglyceridemia, and insulin resistance (1). (cellsignal.com)
  • Caspase 9 (Apoptotic Protease Mch 6 or Apoptotic Protease Activating Factor 3 or ICE Like Apoptotic Protease 6 or CASP9 or EC - Caspase-9 is an initiator caspase encoded by the CASP9 gene. (grandresearchstore.com)
  • To determine DNA damage-induced, p53-mediated apoptosis in spinal cord injury, we performed RT-PCR microarray and analyzed 84 DNA damaging and apoptotic genes. (springer.com)
  • Genes involved in DNA damage and apoptosis were upregulated whereas anti-apoptotic genes were downregulated in injured spinal cords. (springer.com)
  • Thus, current array data showed that most genes expressed in haematopoietic stem cells are developmentally regulated and associated with cell self-renewal 1 as well as survival, differentiation and/or migration/adhesion 2 . (medsci.org)
  • In addition In vivo apoptotic effect of hepatitis B vaccine was observed in mouse liver. (blogspot.com)
  • Lipin 1 plays a role in lipid metabolism in various tissues and cell types including liver, muscle, adipose tissues, and neuronal cell lines (2-4). (cellsignal.com)