Apoptotic Protease-Activating Factor 1: 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.Apoptosis: 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.Caspases: 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.Caspase 3: 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.Caspase 9: 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.Cysteine Endopeptidases: 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.Proto-Oncogene Proteins c-bcl-2: 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.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Enzyme Activation: 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.Cytochrome c Group: 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)Proteins: 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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).bcl-2-Associated X Protein: 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.DNA Fragmentation: 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.Caspase 8: 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.Mitochondria: 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)HIV Protease: 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.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Cytochromes c: 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.Antigens, CD95: 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.In Situ Nick-End Labeling: 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.Apoptosis Regulatory Proteins: 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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Signal Transduction: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cell Survival: 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.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Fas Ligand Protein: 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.Tumor Suppressor Protein p53: 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.Caspase 7: 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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.bcl-X Protein: 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.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cells, Cultured: 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.Caspase 2: 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.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Blotting, Western: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Molecular Sequence Data: 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.Tumor Cells, Cultured: 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.Poly(ADP-ribose) Polymerases: 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.Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Protease La: 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.Amino Acid Sequence: 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.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Necrosis: 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.Flow Cytometry: 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.ATP-Dependent Proteases: 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.Proto-Oncogene Proteins: 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.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Phosphatidylserines: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Caspase 1: 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.Caspase 6: 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.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Membrane Proteins: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Oligopeptides: Peptides composed of between two and twelve amino acids.Mice, Inbred C57BLTransfection: 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.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.HeLa Cells: 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.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Mutation: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.RNA, Messenger: 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.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Protein Binding: 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.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Protein Structure, Tertiary: 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.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.Mitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Macrophages: 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.)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Serpins: 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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Kinetics: The rate dynamics in chemical or physical systems.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein Processing, Post-Translational: 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.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Proteolysis: 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.Cathepsins: 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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.NitrophenolsSequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Mice, Inbred BALB CMice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Caspase 10: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Cloning, Molecular: 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.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Ubiquitin-Specific Proteases: 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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Sulfonamides: A group of compounds that contain the structure SO2NH2.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Proto-Oncogene Proteins c-myc: Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Endopeptidase Clp: 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.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Pepstatins: N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Culture Media, Serum-Free: CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
... apoptotic protease activating factor). The team published their results in an article entitled "Apaf-1, a human protein ... Their observations helped to lead later work toward the genetic pathways of programmed cell death. In a signal article ... Landmark research by David L. Vaux and colleagues described the anti-apoptotic and tumorigenic (tumor-causing) role of the ... It identified and reconstituted the mitochondrial pathway to apoptosis and illuminated whole new avenues of research on ...
Caspase-9 and the Apoptotic Protease Activating factor-1 (APAF1). These components are essential for forming a ternary complex ... called the apoptosome that activates Caspase-3 downstream of the intracellular or mitochondrial pathway of apoptosis. He was ... 103 (1): 7-9. doi:10.1073/pnas.0509187103. PMC 1324996 . PMID 16380419. Zou, H.; Henzel, W. J.; Liu, X.; Lutschg, A.; Wang, X ... 1997-08-08). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of ...
... apoptotic protease activating factor 1) upon mitochondria-mediated apoptosis which must be stimulated by some type of stress ... P53 functions as a tumor suppressor that is involved in preventing cancer and occurs naturally in apoptotic pathways. P53 ... c-dependent Caspase Activation in Ovarian Cancer Cell Lines Due to Diminished or Absent Apoptotic Protease Activating Factor-1 ... Chemotherapies like ionizing radiation have been developed to activate these repressed PCD pathways by hyper-stimulation to ...
Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated ... up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions. ... with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. ... including activation of the coagulation and complement pathways, as well as endothelial dysfunction. Activated protein C helps ...
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins. The two pathways ... Caspase-independent apoptotic pathway There also exists a caspase-independent apoptotic pathway that is mediated by AIF ( ... also called the mitochondrial pathway) and the extrinsic pathway.[16] The intrinsic pathway is activated by intracellular ...
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... Caspase-independent apoptotic pathway. There also exists a caspase-independent apoptotic pathway that is mediated by AIF ( ... Weak external signals may also activate the intrinsic pathway of apoptosis.[7] Both pathways induce cell death by activating ... also called the mitochondrial pathway) and the extrinsic pathway.[18] The intrinsic pathway is activated by intracellular ...
The factor that seems to induce more cell differentiation is caspase-3 protease. This was identified as the penultimate stage ... Cell apoptotic death is a process executed by cysteine proteases that allows the animals to keep their homeostasis, also ... "Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway ... "The Contribution of Apoptosis-inducing Factor, Caspase-activated DNase, and Inhibitor of Caspase-activated DNase to the Nuclear ...
JNK translocates to the nucleus and activates transcription factors such as c-Jun and ATF2. The JNK pathway is involved in cell ... and anti-apoptotic factors. Activation of the MAPK pathways: Of the three major MAPK cascades, TNF induces a strong activation ... Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). Both factors were described ...
epidermal growth factor receptor signaling pathway. • cellular response to growth factor stimulus. • MAPK cascade. • Fc-epsilon ... 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- ... EGFR pathway[edit]. SHC1 has been found to act in signaling information after epidermal growth factor(EGF) stimulation. ...
Caspase stands for cysteine-aspartic acid protease and play an essential role in the apoptotic pathway of the cell. Protease 2A ... protein and other transcription factors at glutamine-glycine sites This inhibition of transcription is caused by Protease 3C, ... which leads to the release of cytochrome C from mitochondria and activating caspase- 9 (Chau). 3C is responsible for the ... Chau, DH (2007). "Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage ...
Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. The ... a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases". Cell Death and ... This extrinsic activation then triggers the hallmark caspase cascade characteristic of the apoptotic pathway, in which caspase- ... In intrinsic activation, cytochrome c from the mitochondria works in combination with caspase-9, apoptosis-activating factor 1 ...
TRAIL-activated apoptotic signaling pathway. • proteolysis. • macrophage differentiation. • TRIF-dependent toll-like receptor ... signaling pathway. • response to tumor necrosis factor. • B cell activation. • cell surface receptor signaling pathway. • ... 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 ...
Knockout or inhibition of apoptotic protease activating factor 1 (APAF1), also results in malformations and increased embryonic ... Besides the above two types of PCD, other pathways have been discovered. Called "non-apoptotic programmed cell-death" (or " ... 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) ...
... MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... "A second serine protease associated with mannan-binding lectin that activates complement". Nature. 386 (6624): 506-510. doi: ... SP-A can also bind to TLR2 (toll-like receptor 2). This interaction causes decrease of TNF-α (tumor necrosis factor-α) ... Collectins SP-A and SP-D enhance clearance of apoptotic cells by macrophages. Collectins are linked with activation of lectin ...
"Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates ... "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 ( ... Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. ... Moreover, the biochemical form of caspase-8 differed in the two pathways. For the death pathway, the caspase-8 zymogen is ...
The pro-apoptotic protease, caspase 3, activates ROCK kinase activity by cleaving the C-terminal PH domain. As a result, the ... elongation factor, translation co-factor), MARCKS (myristylated alanine-rich C kinase substrate), Caponin (unknown function), ... ROCKs also seem to antagonize the insulin signaling pathway, resulting in a reduction of cell size and influence cell fate. ... Active ROCK in these cells seems to stimulate the disruption of E-Cadherin-mediated cell-cell contacts by activating actomyosin ...
B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway. ... Identification of the MDM2 oncoproteinas a substrate for CPP32-like apoptotic proteases. J. Biol. Chem. 272:15049-15052. Lopes ... apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFkappaB transcription factors ... Mammalian transcription factor LSF is a target of ERK signaling. J. Cell. Biochem. 89:733-746. Hartley, D. and Cooper, G.M. ...
A reactive center loop of the protease is bound to the central beta loop of the serpin, trapping the protease in a state where ... Apoptosis can be triggered through two main pathways; extrinsic and intrinsic. The extrinsic pathway mostly involves ... Bcl-2 is the most well known of the anti-apoptotic members, and is classified as an oncogene. Studies have shown that the Bcl-2 ... After several stimuli leading to cell death are activated, BAX also moves to the mitochondria where it carries out its ...
... proteases, and thus the apoptotic cascade. Additional sources of neuronal cell death related to excitotoxicity involve energy ... This treatment aims to limit the apoptosis of cerebral neurons caused by various pathways related to excitotoxicity, free ... 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, ...
... which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD. Overall, ... "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates ... or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907-15. doi:10.1074/jbc. ... It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic ...
In the activation pathway illustrated to the left, the ligand involved is a cytokine and the specific kinase taking part in ... 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 ...
... intact apoptotic cells, as well as cell debris by phagocytes. The complement system can be activated through three pathways: ... which have protease domains. There are also sMAP (also called MAp19) and MAp44, which do not have protease domains and are ... It is produced in the liver as a response to infection, and is part of many other factors termed acute phase proteins. ... the alternative pathway, and the lectin pathway. One way that the most-recently discovered lectin pathway is activated is ...
A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase ... transcription factor. Phosphorylated CREB translocates into the nucleus and mediates increased expression of anti-apoptotic ... This form of NGF is also referred to as proNGF (NGF precursor). The gamma subunit of this complex acts as a serine protease, ... are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. The activated transcription factor c- ...
1997). "Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that ... activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486-91. doi:10.1073/pnas.93.25. ... Zheng, L; Schickling O; Peter M E; Lenardo M J (August 2001). "The death effector domain-associated factor plays distinct ... 1996). "Mch3, a novel human apoptotic cysteine protease highly related to CPP32". Cancer Res. 55 (24): 6045-52. PMID 8521391. ...
7 are effector proteases whereas caspase-8 is an initiator caspase that sits more upstream in the apoptotic pathway. These ... activates signaling pathways to commit suicide. The membrane permeability of the mitochondria increases and particular proteins ... a novel cell surface receptor for the protease factor Xa". J. Biol. Chem. 269 (5): 3139-42. PMID 8106347. Maruyama K, Sugano S ... This suggests that down-regulation of survivin by p53 is important for p53-mediated apoptotic pathway to successfully result in ...
... (from the Greek νέκρωσις "death, the stage of dying, the act of killing" from νεκρός "dead") is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal. Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated, and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space. This initiates in the surrounding tissue an inflammatory response which attracts leukocytes and nearby ...
The precise way in which the presence of NDV induces tumor cell death remains to be clarified and may show variation regarding the strains of NDV used and which type of cancer is targeted. NDV triggers apoptosis[17] in a wide range of cancer cell types via the mitochondrial/intrinsic pathway, through loss of membrane potential and thereby inducing release of cytochrome c in the tumor cell. The results[17] also indicate the extrinsic pathway is activated by TNF-related, apoptosis-inducing ligand-induced, NDV-mediated apoptosis in a late stage. Another study[20] found a hyperfusogenic NDV/F3aa(L289A) with refined abilities to fuse into somatic cells. NDV has aggregating properties causing syncytia formations of tumor cells, which, apart from amplifying immune-based cell killing, also results in necrosis of cells. This pathway was believed to lead to a considerable boost of immune activation and potentially an antitumor response, which was supported by ...
Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see "Controlling the Caspases", by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001). When a cell receives an apoptotic stimulus, IAP activity is relieved after SMAC (Second Mitochondria-derived Activator of Caspases, or its mouse homolog, called DIABLO), a mitochondrial protein, is reléased into the cytosol. SMAC binds to IAPs, and in doing so "inhibits the inhibitors", effectively preventing them from arresting the apoptotic process. But before we go on to a short description of how SMAC is reléased, lets take a look at two well-studied extrinsically induced apoptotic processes: the TNF and the Fas pathways. Keep in mind, however, that both activating and inhibiting factors are present at éach step of these pathways. Tumor ...
... , or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis[1] or apoptosis.[2] It is followed by karyorrhexis, or fragmentation of the nucleus. Pyknosis (from Greek pyknono meaning "to thicken up, to close or to condense") is also observed in the maturation of erythrocytes (a red blood cell) and the neutrophil (a type of white blood cell). The maturing metarubricyte (a stage in RBC maturation) will condense its nucleus before expelling it to become a reticulocyte. The maturing neutrophil will condense its nucleus into several connected lobes that stay in the cell until the end of its cell life. Pyknotic nuclei are often found in the zona reticularis of the adrenal gland. They are also found in the keratinocytes of the outermost layer in parakeratinised epithelium. ...
... is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. Kinds of cell death include the following: Programmed cell death (or PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and metazoa (multicellular animals) tissue development. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or ...
... (or PCD) is the death of a cell in any form, mediated by an intracellular program. PCD is carried out in a biological process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death, but necrosis was long seen as a non-physiological process that occurs as a result of infection or injury. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of programmed cell death. It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is ...
Apoptosis (dari bahasa Yunani apo = "dari" dan ptosis = "jatuh") adalah mekanisme biologi yang merupakan salah satu jenis kematian sel terprogram.[1] Apoptosis digunakan oleh organisme multisel untuk membuang sel yang sudah tidak diperlukan oleh tubuh.[1] Apoptosis berbeda dengan nekrosis dan piroptosis.[2] Apoptosis pada umumnya berlangsung seumur hidup dan bersifat menguntungkan bagi tubuh, sedangkan nekrosis adalah kematian sel yang disebabkan oleh kerusakan sel secara akut; dan proptosis adalah kematian sel terprogram yang terjadi pada infeksi patogen intraseluler dan menimbulkan inflamasi.[2] Contoh nyata dari keuntungan apoptosis adalah pemisahan jari pada embrio.[3] Apoptosis yang dialami oleh sel-sel yang terletak di antara jari menyebabkan masing-masing jari menjadi terpisah satu sama lain.[3] Bila sel kehilangan kemampuan melakukan apoptosis maka sel tersebut dapat membelah secara tak terbatas dan akhirnya menjadi kanker.[4]. Apoptosis memiliki ciri morfologis yang khas seperti membran ...
An etoposide-treated DU145 prostate cancer cell exploding into a cascade of apoptotic bodies. The sub images were extracted from a 61-hour time-lapse microscopy video, created using quantitative phase-contrast microscopy. The optical thickness is color-coded. With increasing thickness, color changes from gray to yellow, red, purple and finally black.[1] ...
The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues.[3]. Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis. These forms of cell death are important for protecting an organism from stress signals and pathogenic attack. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. These are signalling molecules that allow recruitment of immune cells to an infected cell or tissue. There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon ...
Odes, Edward J.; Randolph-Quinney, Patrick S.; Steyn, Maryna; Throckmorton, Zach; Smilg, Jacqueline S.; Zipfel, Bernhard; Augustine, Tanya N.; Beer, Frikkie de; Hoffman, Jakobus W.; Franklin, Ryan D.; Berger, Lee R.; Sciences, School of Anatomical; Witwatersrand, University of the; Africa, South; Institute, Evolutionary Studies; Geosciences, School of; Witwatersrand, University of the; Africa, South; Sciences, School of Anatomical; Witwatersrand, University of the; Africa, South; Institute, Evolutionary Studies; Geosciences, School of; Witwatersrand, University of the; Africa, South; Sciences, School of Forensic and Applied; Lancashire, University of Central; Kingdom, United; Sciences, School of Anatomical; Witwatersrand, University of the; Africa, South; Institute, Evolutionary Studies; Geosciences, School of; Witwatersrand, University of the; Africa, South; Medicine, De Busk College of Osteopathic; University, Lincoln Memorial; Institute, Evolutionary Studies; Geosciences, School of; ...
Hormon (Yun. horman - "sangkan ojah") hartina utusan kimiawi ti hiji sél (atawa sagolongan sél) ka sél lianna. Sakabéh organisme multisélular ngahasilkeun hormon (kaasup tutuwuhan - baca artikel fitohormon). Hormon nu paling dipikawanoh ti bangsa sasatoan (jeung manusa) nyaéta nu dihasilkeun ku kelenjar éndokrin vertebrata, padahal hormon téh dihasilkeun ku ampir unggal sistim organ jeung jaringan. Molekul hormon disékrésikeun (dikaluarkeun) langsung kana aliran getih, cairan awak lianna, atawa kana jaringan anu tangtu. Pindahna ku cara sirkulasi atawa difusi ka sél targétna, nu bisa baé sél nu padeukeut/natangga (aksi parakrin) dina jaringan nu sarua atawa sél nu ayana di organ séjén. Fungsi hormon nyaéta salaku sinyal/iber ka sél targét; peta hormon ditangtukeun ku pola sékrési jeung transduksi sinyal jaringan nu nampana. Hormon petana rupa-rupa, ngawengku stimulasi/pangrangsang atawa inhibisi/meungpeuk kamekaran, induksi atawa suprési apoptosis (program paéh sél), ...
தின்குழியமை என்பது விழுங்கி அழிக்கும் செயல்முறையைக் குறிக்கும். பெருவிழுங்கியின் முக்கியமான தொழில்களில் ஒன்று நுரையீரலில் முதிர்ச்சியடையாமலே புறக்காரணிகளால் இறந்து போகும் கலங்களை (necrotic cells) 'விழுங்கி அழித்தல்' மூலம் அகற்றுதல் ஆகும். நீடித்த அழற்சி நிலைகளில், இவ்வாறு இறந்த கலங்கள் அகற்றப்படுவது அவசியமாகும். பழுதுபட்ட கலங்கள், சிதைந்த கலங்களை, இப்படியான விழுங்கும் ...
അമേരിക്കയിൽ കണ്ടു വരുന്ന, മാർജ്ജാരവർഗ്ഗത്തിൽപ്പെടുന്ന ഒരു വലിയ ജീവിയാണ്‌ പൂമ.(പുമ)[3] ഇംഗ്ലീഷ്:Puma. ഏറ്റവും അധികം പേരുകളുള്ള മൃഗം എന്ന ഗിന്നസ് റെക്കോഡുണ്ട് ഇതിന്. കൂഗർ, പാന്തർ, പ്യൂമ, മൗണ്ടൻ ലയൺ, മൗണ്ടൻ ക്യാറ്റ് തുടങ്ങി നാൽപ്പതോളം പേരുകളിൽ അറിയപ്പെടുന്നു. കടുവ, സിംഹം, ജാഗ്വർ എന്നിവക്ക് പിന്നിലായി പുലിക്കൊപ്പം പൂച്ച കുടുംബത്തിലെ ഏറ്റവും വലിയ നാലാമത്തെ ജീവിയാണ് പൂമ. എങ്കിലും ...
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the ... apoptotic signaling pathway Source: InterPro. *regulation of apoptotic process Source: InterPro. View the complete GO ... Apoptotic protease-activating factor 1UniRule annotation. ,p>Information which has been generated by the UniProtKB automatic ... tr,G3XA09,G3XA09_MOUSE Apoptotic protease-activating factor 1 OS=Mus musculus OX=10090 GN=Apaf1 PE=1 SV=1 ...
Apoptotic Protease-Activating Factor 1 / metabolism * Cytochromes c / genetics* * Female * Genetic Linkage ... A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia Nat Genet. 2008 Apr; ... The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other ... Ian M Morison 1 , Elisabeth M Cramer Bordé, Emma J Cheesman, Pak Leng Cheong, Andrew J Holyoake, Serge Fichelson, Robert J ...
... activating cascade of caspases involving caspases 12 and 3. Conclusively, the damages caused by Glu and Hcy to PC12 cells can ... The mechanisms of action include: (1) increasing calcium influx; (2) producing ROS; (3) initiating lipid peroxidation; (4) ... apoptotic protease activating factor 1). ... The three pathways eventually trigger neuronal apoptotic cell ... the intrinsic pathway) (Figure 6) [40]; (2) indirectly activate caspase-3 through the activation of caspase-12 (the ER-pathway ...
In mammalian cells, the apoptotic machinery is activated mainly via two pathways: the extrinsic pathway, through the engagement ... apoptotic protease-activating factor 1. B-CLL. B-cell chronic lymphoblastic leukemia. BH3. Bcl-2 homology domain 3. DEVD-AMC. ... Requirement of Apoptotic Protease-Activating Factor-1 for Bortezomib-Induced Apoptosis but Not for Fas-Mediated Apoptosis in ... Requirement of Apoptotic Protease-Activating Factor-1 for Bortezomib-Induced Apoptosis but Not for Fas-Mediated Apoptosis in ...
The Apoptotic Protease-Activating Factor 1-Mediated Pathway of Apoptosis Is Dispensable for Negative Selection of Thymocytes ... Evidence for Involvement of the p44/42 Mitogen-Activated Protein Kinase Pathway Miriam Wittmann, Petra Kienlin, Susanne Mommert ... Activating Immunity in the Liver. II. IFN-β Attenuates NK Cell-Dependent Liver Injury Triggered by Liver NKT Cell Activation ... The State of CD4+ T Cell Activation Is a Major Factor for Determining the Kinetics and Location of T Cell Responses to Oral ...
... apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation). ... Other CARD proteins participate in NF-kappaB signalling pathways associated with innate or adaptive immune responses. Proteins ... The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the ... and anti-apoptotic proteins; many of these proteins are also involved in controlling cellular activation and proliferation ...
Cyt c in the cytosol catalyzes the oligomerization of apoptotic protease activating factor-1. This promotes the activation of ... B, Pathways of PCD in tobacco cells. H2O2 or SA induce a mitochondria-dependent pathway in which cyt pathway function is ... Cyt Pathway Capacity. In vivo and in organello assays were used to estimate the functional state of the cyt pathway (see " ... Anti-apoptotic Bcl-2 family members act to prevent cyt c release, whereas pro-apoptotic Bcl-2 family members promote such ...
... cytochrome c complexes with apoptosis-protease activating factor-1, which, in the presence of ATP, leads to activation of the ... Essential in this process is the caspase family of cysteine proteases (2). Signals activating the "intrinsic apoptotic pathway ... Proinflammatory Cytokines Activate the Intrinsic Apoptotic Pathway in β-Cells. Lars G. Grunnet, Reid Aikin, Morten F. Tonnesen ... Proinflammatory Cytokines Activate the Intrinsic Apoptotic Pathway in β-Cells. Lars G. Grunnet, Reid Aikin, Morten F. Tonnesen ...
Following release, cytochrome c binds to the apoptotic protease activating factor-1 (APAF-1) and activates the caspase cascade ... apoptotic pathway [151]. Evidence also exists for the activation of extrinsic apoptotic pathway in Aβ-evoked death. In cortical ... 5. Sphingomyelin/Ceramide Pathway as a Therapeutic Approach in AD. Due to plethora of intrinsic factors affecting AD, it is ... Ceramide accumulation increases the interaction between p75NTR, NGF, and ceramides and activates β-secretase pathway in APP ...
... apoptotic protease activating factor; IAP: inhibitor of apoptosis.. The extrinsic or death receptor pathway. The extrinsic or ... independently activates the two important anti-apoptotic pathways in lung fibroblasts: the focal adhesion kinase (FAK) pathway ... Transforming growth factor (TGF)-β1 stimulates pulmonary fibrosis and inflammation via a Bax-dependent, Bid-activated pathway ... As previously mentioned, TGF-β activates the FAK and the PI3K/Akt anti-apoptotic pathways in lung fibroblasts 25. ...
... apoptotic protease-activating factor 1) to activate caspase-9. The death receptor pathway is activated when ligands of the ... The two pathways are largely independent, but in certain cells the death receptor pathway engages the stress pathway via a ... Pathways to cell death. The stress pathway is initiated by BH3-only proteins (BH3), which inactivate the Bcl-2-like proteins ... Differing binding profiles and apoptotic potency of BH3-only proteins. (a) The ability of Bim, Puma and tBid to engage all the ...
Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing ... Factor Pathway in Mouse Insulinoma Cells. Xin Fang, Xiao-liang Miao, Jun-li Liu, Dong-wei Zhang, Min Wang, Dan-dan Zhao, Qian- ... Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways. Ya-yun Qian ...
Apoptotic protease-activating factor 1, KIAA0413 Gene ID 317 NCBI Accession NP_001151 ... Pathways p53 Signaling, Apoptosis, Caspase Cascade in Apoptosis, Tube Formation, Positive Regulation of Endopeptidase Activity ... Apoptotic peptidase activating factor 1, also known as APAF1, is a protein which in humans is encoded by the APAF1 gene. This ... Apoptotic Peptidase Activating Factor 1 (APAF1) Antibodies show synonyms for this antigen * APAF1 ...
Neuroprotection against hypoxic-ischemic brain injury by inhibiting the apoptotic protease activating factor-1 pathway. Stroke ... Vosler, P.S., Kass, J.I., Wang, E.W. and Snyderman, C.H. (2016). Successful implementation of a clinical care pathway for ... Calcium dysregulation induces apoptosis-inducing factor release: Cross-talk between PARP-1 and calpain-signaling pathways. ... Delayed hypothermia preferentially increases expression of brain-derived neurotrophic factor exon III in rat hippocampus after ...
In this pathway, caspase-9 is activated when complexed with extramitochondrial cytochrome c and apoptotic protease activating ... It has been shown that bryo1 treatment activates PKC and induced nuclear factor-κB activation in a number of leukemic and tumor ... Inhibition of ubiquitin-proteasome pathway activates a caspase-3 (CPP32)-like protease and induces Bcl-2 cleavage in human M- ... During apoptosis, several effector proteases such as caspase-3 mediate the deliberate disassembly of the cell into apoptotic ...
Neuronal death was mediated via alteration of apoptotic protease-activating factor (Apaf-1) expression that in turn induced ... Fran, it is possible that TNF signaling in the brain antagonizes trophic factor pathways (insulin-like growth factor-1, or IGF- ... and p38 MAPK pathways. Depending on cellular context, R1 and R2 can activate many of the same downstream pathways and act ... Greg, Im not surprised, as TNF signaling to apoptotic pathways may be stronger than the opposing NFκB counterarm depending on ...
... apoptotic protease activating factor). The team published their results in an article entitled "Apaf-1, a human protein ... Their observations helped to lead later work toward the genetic pathways of programmed cell death. In a signal article ... Landmark research by David L. Vaux and colleagues described the anti-apoptotic and tumorigenic (tumor-causing) role of the ... It identified and reconstituted the mitochondrial pathway to apoptosis and illuminated whole new avenues of research on ...
Caspase-9 and the Apoptotic Protease Activating factor-1 (APAF1). These components are essential for forming a ternary complex ... called the apoptosome that activates Caspase-3 downstream of the intracellular or mitochondrial pathway of apoptosis. He was ... 103 (1): 7-9. doi:10.1073/pnas.0509187103. PMC 1324996 . PMID 16380419. Zou, H.; Henzel, W. J.; Liu, X.; Lutschg, A.; Wang, X ... 1997-08-08). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of ...
... superfamily of cytokines represents a multifunctional group proinflammatory cytokines which activate signaling pathways for ... On the other hand, TNFR2 is primarily expressed in immune cells and is activated by both TNFα and TNFβ1. ... Induction of cellular responses to Tumor Necrosis Factor occurs through two receptors, TNFR1 (TNF Receptor-1 or CD120a) and ... TNFR2 (TNF Receptor-2 or CD120b). TNFR1 is activated in most human tissues by the binding of TNFα. ...
Released cytochrome c interacts with apoptotic protease-activating factor 1, ATP, and pro-caspase 9 to form the apoptosome. ... Mitochondrial membrane potential (ΔΨ) disruption and ATP depletion are two key steps toward STS-induced apoptotic pathway ... The higher the STS dose used, the earlier the apoptotic process started, and the earlier the caspase 3 was activated. ... a biopsy specimen combined with in vitro assays is often used to detect apoptotic signals in certain molecular pathways ...
... survival advantage conferred by mutations in apoptotic signaling pathway components. Apoptotic protease activating factor 1 ( ... apoptosis-inducing factor (aif) is a mediator of an alternate, independent apoptotic pathway (Cande et al., 2002). The apaf1 ... achieved through a reduction in primitive NSC death mediated by these apoptotic pathways, then the survival factor effect ... pathway responsible for mediating cell death in these cultures was the apaf1-cas9 apoptotic pathway, although there was still ...
... "apoptotic protease activating factor-1"). ... Since the pathway through apoptosis is very long if one ... Caspase-9 is a protease that cleaves proteins.. *As caspase-9 cleaves proteins, it activates other caspases from its family. ... For example: The withdrawal of growth factors of neurons will cause apoptosis because the growth factors serve as positive ... 1.2 Required factors for cells apoptosis to occur. *1.3 The mechanism of apoptosis *1.3.1 Apoptosis triggered by internal ...
... which may also reflect a decrease in the expression of death receptors and apoptotic protease-activating factor 1 (Apaf-1) (SI ... In mammals, there are two major apoptosis pathways (15). The intrinsic apoptosis pathway is regulated by p53 and proapoptotic ... Expression of death receptor genes and apoptotic protease-activating factor 1 (APAF-1) is also controlled by p53 (19, 20). ... could similarly activate transcription of CDKN1A and apoptotic genes and thereby induce cell cycle arrest and apoptosis (refer ...
ER stress activates both intrinsic and extrinsic apoptotic pathways [13, 14]. Currently, three main pathways of ER stress- ... Activated ATF6 translocates to the Golgi, cleaved by proteases to form an active 50 kDa fragment. ATF6 p50 and XBP1 bind ER ... CHOP down-regulates the anti-apoptotic factor B cell lymphoma-2 (Bcl-2), but also upregulates Ero-1, a thiol oxidase that ... There are two main apoptotic pathways: the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway [21 ...
Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during ... Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and ... Inhibition of apoptotic signaling cascades causes loss of trophic factor dependence during neuronal maturation. J. Cell Biol. ... Neurons can use the E2F1 pathway to reach their apoptotic threshold by inducing the expression of Bim (Biswas et al., 2005) and ...
  • 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)
  • 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)
  • . GADD45alpha/beta triggers apoptosis through activation of mitogen-activated protein kinase kinase kinase 4 ( MEKK4 )/ mitogen-activated protein kinase kinase 4 ( MKK4 ) or mitogen-activated protein kinase kinase 7 ( MKK7 )/ c-Jun N-terminal kinase/stress-activated protein kinase ( JNK ) cascade and/or MEKK4 / MKK4 or MKK7 / mitogen-activated protein kinase 14 ( p38 alpha ) cascade. (bio-rad.com)
  • Among them, the Ras-Raf-MEK-ERK/mitogen-activated protein kinase (MAPK) pathway and the Ras-PI3K-Akt (also known as protein kinase [PK]B) pathway are vital for cell proliferation and cell survival. (ahajournals.org)
  • Apoptotic cell death is characterised by a series of morphological and biochemical changes such as plasma membrane blebbing, chromatin condensation, internucleosamal DNA cleavage and exposure of phospatidyl serine on the extracellular side of the plasma membrane. (biologists.org)
  • It is also reported recently that Hsp90 protects beclin-1 (Atg6), a key autophagy-promoting protein that regulates the formation of autophagosomes from ubiquitination-associated proteolytic degradation ( 11 ). (aacrjournals.org)
  • 2 The APC anticoagulant pathway is mediated by proteolytic inactivation of blood coagulation Factors Va and VIIIa with the contribution of several cofactors, including protein S, high density lipoproteins, phosphatidylserine, cardiolipin, and glucosylceramide to name a few. (ahajournals.org)
  • Picornaviruses are single-stranded RNA viruses that modify the host cell apoptotic response, probably in order to promote viral replication, largely as a function of the viral proteases 2A, 3C, and 3CD. (asm.org)
  • The ability of AOX to attenuate these death pathways may relate to its ability to maintain mitochondrial function after insult with a death-inducing compound or may relate to its ability to prevent chronic oxidative stress within the mitochondrion. (plantphysiol.org)
  • Oxidative stress is one of the most common mechanisms of cachexia caused by different factors. (hindawi.com)
  • Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. (aacrjournals.org)
  • When the primary metabolic pathway for ATP production (oxidative phosphorylation) is blocked, for example by the absence of an electron acceptor, energy utilization must be curtailed simultaneously. (biologists.org)
  • This study aimed to investigate the mechanism of oxidative stress-mediated apoptosis caused by NH 3 in chicken livers and whether miR-187-5p/apaf-1 axis was involved in this mechanism. (ovid.com)
  • Altogether, miR-187-5p/apaf-1 axis participated in oxidative stress-mediated apoptosis caused by NH 3 via mitochondrial pathway in the livers of chickens for fattening. (ovid.com)
  • p66SHC functionally is also involved in regulating oxidative and stress- induced apoptosis - mediating steroid action through the redox signaling pathway. (wikipedia.org)
  • The absence of sufficient anti-apoptotic protein expression (dotted green lines) is proposed to tip the balance in favor of activating pro-apoptotic pathways (solid red lines). (psu.edu)
  • Bcl-XL is a major anti-apoptotic protein in the Bcl2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. (ufl.edu)