Apoptotic Protease-Activating Factor 1
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.
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.
Caspase 3
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
Cysteine Proteinase Inhibitors
Enzyme Activation
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.
Cytochrome c Group
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
HIV Protease
Serine Endopeptidases
Peptide Hydrolases
Endopeptidases
Cysteine Proteases
Protease La
ATP-Dependent Proteases
Amino Acid Sequence
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.
Protease Nexins
DNA Fragmentation
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.
Substrate Specificity
bcl-2-Associated X Protein
Caspase Inhibitors
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.
Cells, Cultured
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)
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.
Phagocytosis
Cell Survival
Cathepsins
Jurkat Cells
Amino Acid Chloromethyl Ketones
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.
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.
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.
Blotting, Western
Base Sequence
Annexin A5
Mutation
Apoptosis Regulatory Proteins
Ubiquitin-Specific Proteases
Cytochromes c
Tumor Cells, Cultured
Cell Death
Phosphatidylserines
Endopeptidase Clp
Aspartic Acid Endopeptidases
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.
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.
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.
Binding Sites
Pepstatins
Protein Binding
Chymotrypsin
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.
Membrane Proteins
Trypsin
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.
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.
Sequence Homology, Amino Acid
Proteolysis
Tumor Suppressor Protein p53
Poly(ADP-ribose) Polymerases
bcl-X Protein
Cloning, Molecular
Caspase 6
Models, Molecular
Electrophoresis, Polyacrylamide Gel
Caspase 7
Enzyme Inhibitors
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.
Cathepsin L
Peptide Fragments
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.)
HeLa Cells
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.
Pancreatic Elastase
Trypsin Inhibitors
Escherichia coli
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Transfection
Dose-Response Relationship, Drug
Proto-Oncogene Proteins
C. elegans MAC-1, an essential member of the AAA family of ATPases, can bind CED-4 and prevent cell death. (1/406)
In the nematode Caenorhabditis elegans, CED-4 plays a central role in the regulation of programmed cell death. To identify proteins with essential or pleiotropic activities that might also regulate cell death, we used the yeast two-hybrid system to screen for CED-4-binding proteins. We identified MAC-1, a member of the AAA family of ATPases that is similar to Smallminded of Drosophila. Immunoprecipitation studies confirm that MAC-1 interacts with CED-4, and also with Apaf-1, the mammalian homologue of CED-4. Furthermore, MAC-1 can form a multi-protein complex that also includes CED-3 or CED-9. A MAC-1 transgene under the control of a heat shock promoter prevents some natural cell deaths in C. elegans, and this protection is enhanced in a ced-9(n1950sd)/+ genetic background. We observe a similar effect in mammalian cells, where expression of MAC-1 can prevent CED-4 and CED-3 from inducing apoptosis. Finally, mac-1 is an essential gene, since inactivation by RNA-mediated interference causes worms to arrest early in larval development. This arrest is similar to that observed in Smallminded mutants, but is not related to the ability of MAC-1 to bind CED-4, since it still occurs in ced-3 or ced-4 null mutants. These results suggest that MAC-1 identifies a new class of proteins that are essential for development, and which might regulate cell death in specific circumstances. (+info)Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. (2/406)
The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development. (+info)CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. (3/406)
We have identified and characterized CIPER, a novel protein containing a caspase recruitment domain (CARD) in its N terminus and a C-terminal region rich in serine and threonine residues. The CARD of CIPER showed striking similarity to E10, a product of the equine herpesvirus-2. CIPER formed homodimers via its CARD and interacted with viral E10 but not with several apoptosis regulators containing CARDs including ARC, RAIDD, RICK, caspase-2, caspase-9, or Apaf-1. Expression of CIPER induced NF-kappaB activation, which was inhibited by dominant-negative NIK and a nonphosphorylable IkappaB-alpha mutant but not by dominant-negative RIP. Mutational analysis revealed that the N-terminal region of CIPER containing the CARD was sufficient and necessary for NF-kappaB-inducing activity. Point mutations in highly conserved residues in the CARD of CIPER disrupted the ability of CIPER to activate NF-kappaB and to form homodimers, indicating that the CARD is essential for NF-kappaB activation and dimerization. We propose that CIPER acts in a NIK-dependent pathway of NF-kappaB activation. (+info)mE10, a novel caspase recruitment domain-containing proapoptotic molecule. (4/406)
Apoptotic signaling is mediated by homophilic interactions between conserved domains present in components of the death pathway. The death domain, death effector domain, and caspase recruitment domain (CARD) are examples of such interaction motifs. We have identified a novel mammalian CARD-containing adaptor molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits significant homology (47% identity and 64% similarity) to the CARD of a gene from Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis indicates that CARD-mediated mE10 oligomerization is essential for killing activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and promoted its processing to the active dimeric species. Taken together, these data suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by mE10-induced oligomerization. (+info)Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1. (5/406)
Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This is despite indications that remnant apoptotic events are detected following exercise, muscle injury and the progression of dystrophinopathies. The recent elicitation of a cytochrome c-mediated induction of caspases has led to speculation regarding a cytochrome c mechanism in muscle. We demonstrate that cytosols from skeletal muscle biopsies from healthy human volunteers lack the ability to activate type-II caspases by a cytochrome c-mediated pathway despite the confirmed presence of both procaspase-3 and -9. This was not due to the presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase activity when added to a control cytosol, subsequently activated by cytochrome c and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These data indicate that human skeletal muscle cells will be refractory to mitochondrial-mediated events leading to apoptosis and thus can escape a major pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation of cell survival in the presence of the profusion of mitochondria required for energy generation in motility. (+info)An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. (6/406)
We report here the reconstitution of the de novo procaspase-9 activation pathway using highly purified cytochrome c, recombinant APAF-1, and recombinant procaspase-9. APAF-1 binds and hydrolyzes ATP or dATP to ADP or dADP, respectively. The hydrolysis of ATP/dATP and the binding of cytochrome c promote APAF-1 oligomerization, forming a large multimeric APAF-1.cytochrome c complex. Such a complex can be isolated using gel filtration chromatography and is by itself sufficient to recruit and activate procaspase-9. The stoichiometric ratio of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated, caspase-9 disassociates from the complex and becomes available to cleave and activate downstream caspases such as caspase-3. (+info)Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. (7/406)
The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-kappaB activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-kappaB and apoptotic signaling pathways and may be a component of the host innate immune response. (+info)Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. (8/406)
Mistletoe lectin I (ML-I) is a major active component in plant extracts of Viscum album that is increasingly used in adjuvant cancer therapy. ML-I exerts potent immunomodulating and cytotoxic effects, although its mechanism of action is largely unknown. We show that treatment of leukemic T- and B-cell lines with ML-I induced apoptosis, which required the prior activation of proteases of the caspase family. The involvement of caspases is demonstrated because (a) a peptide caspase inhibitor almost completely prevented ML-I-induced cell death and (b) proteolytic activation of caspase-8, caspase-9, and caspase-3 was observed. Because caspase-8 has been implicated as a regulator of apoptosis mediated by death receptors, we further investigated a potential receptor involvement in ML-I-induced effects. Cell death triggered by ML-I was neither attenuated in cell clones resistant to CD95 nor in cells that were rendered refractory to other death receptors by overexpressing a dominant-negative FADD mutant. In contrast, ML-I triggered a receptor-independent mitochondria-controlled apoptotic pathway because it rapidly induced the release of cytochrome c into the cytosol. Because ML-I was also observed to enhance the cytotoxic effect of chemotherapeutic drugs, these data may provide a molecular basis for clinical trials using MLs in anticancer therapy. (+info)
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APAF1
Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene. This gene encodes a ... Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (Apr 2005). "Structure of the apoptotic protease-activating factor 1 bound to ... Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome ... Overview of all the structural information available in the PDB for UniProt: O14727 (Apoptotic protease-activating factor 1) at ...
Programmed cell death
Knockout or inhibition of apoptotic protease activating factor 1 (APAF1), also results in malformations and increased embryonic ... An atrophic factor is a force that causes a cell to die. Only natural forces on the cell are considered to be atrophic factors ... Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ... Solomon M, Belenghi B, Delledonne M, Menachem E, Levine A (1999). "The involvement of cysteine proteases and protease inhibitor ...
Cytochrome c
Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1). Cytochrome c ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 ... The release of cytochrome-c from mitochondria to the cytosol, where it activates the caspase family of proteases is believed to ... One of the ways cell apoptosis is activated is by release of cytochrome c from the mitochondria into cytosol. A study has shown ...
History of apoptosis research
... apoptotic protease activating factor). The team published their results in an article entitled "Apaf-1, a human protein ... Landmark research by David L. Vaux and colleagues described the anti-apoptotic and tumorigenic (tumor-causing) role of the ... Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (August 1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates ... 39: 1-10. doi:10.1042/bse0390001. PMID 14585070. Diamantis, Aristidis; Magiorkinis, Emmanouil; Sakorafas, George H.; Androutsos ...
Xiaodong Wang (biochemist)
Caspase-9 and the Apoptotic Protease Activating factor-1 (APAF1). These components are essential for forming a ternary complex ... 103 (1): 7-9. doi:10.1073/pnas.0509187103. PMC 1324996. PMID 16380419. Zou, H.; Henzel, W. J.; Liu, X.; Lutschg, A.; Wang, X. ( ... called the apoptosome that activates Caspase-3 downstream of the intracellular or mitochondrial pathway of apoptosis. He was ... 1997-08-08). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of ...
Apoptosome
... apoptotic protease activating factor 1) upon mitochondria-mediated apoptosis which must be stimulated by some type of stress ... c-dependent caspase activation in ovarian cancer cell lines due to diminished or absent apoptotic protease activating factor-1 ... Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis ... By activating the apoptosome by an outside stimulus apoptosis can occur and get rid of the mutated cells. Numerous approaches ...
Apoptosis
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate ... Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C. Pathological inactivation of apoptosis in ... Before the apoptotic cell is disposed of, there is a process of disassembly. There are three recognized steps in apoptotic cell ...
Purpura fulminans
Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated ... with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. ... not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti- ... Kondaveeti S, Hibberd ML, Booy R, Nadel S, Levin M (1999). "Effect of the Factor V Leiden mutation on the severity of ...
CARD domain
Ice protease-activating factor, also known as NLR family, card domain containing 4 (NLRC4), CARD, LRR, and NACHT-containing ... apoptotic peptidase activating factor 1 (also called CED4) [26][permanent dead link] GLAVA1: glavaris peptidase activating ... The adaptor protein VISA further activates the inhibitor of nuclear factor kappa-B kinase (IKK)-protein-kinase family members. ... Activating mutations in at least two related PYD-containing proteins, cryopyrin/CIAS-1 and pyrin/MEFV, have been linked to ...
Apoptosis
Once cytochrome c is released it binds with Apoptotic protease activating factor - 1 (Apaf-1) and ATP, which then bind to pro- ... which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate ... Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C.[80] Pathological inactivation of apoptosis ... There also exists a caspase-independent apoptotic pathway that is mediated by AIF (apoptosis-inducing factor).[43] ...
Caspase-activated DNase
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 ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene ...
B13R (virus protein)
SPI-2 expression also inhibits the apoptotic pathway activated by Fas-ligand and TNFα. Deletion of SPI-2 leads to virus ... SPI-2 is one of these immunomodulatory factors. SPI-2 is a nonglycosylated peptide with size of 38,5 kDa. It is expressed in an ... SPI-2 belongs in superfamily of the inhibitors of serine proteases (serpins). Serpins are the most broadly distributed family ... In mammals serpins are secreted in plasma where they serve as inhibitors of proteases involved in blood coagulation, ...
SHC1
regulation of epidermal growth factor-activated receptor activity. • regulation of growth. • Ras protein signal transduction. • ... When the coagulated protease-activated protein C inhibits p66SHC a cytoprotective effect on diabetic nephropathy is placed on ... negative regulation of apoptotic process. • positive regulation of MAPK cascade. • negative regulation of transcription, DNA- ... epidermal growth factor receptor signaling pathway. • cellular response to growth factor stimulus. • MAPK cascade. • Fc-epsilon ...
Tumor necrosis factor
... which then activates JNK. JNK translocates to the nucleus and activates transcription factors such as c-Jun and ATF2. The JNK ... 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 ...
Picornain 3C
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 ... Therefore, protease 3C depends on poliovirus 3CD protein for the translocation of 3C protease to carry out transcription ...
Mannan-binding lectin
... 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. ... a serine protease called MASP (MBL-associated serine protease). There are three MASPs: MASP-1, MASP-2 and MASP-3, ...
Stress granule
... granule formation is often downstream of the stress-activated phosphorylation of eukaryotic translation initiation factor eIF2α ... and the pro-apoptotic kinase ROCK1. RNA phase transitions driven in part by intermolecular RNA-RNA interactions may play a role ... and because the aggregates are resistant to proteases. It has also been proposed that microtubules play a role in the formation ... Delestienne N, Wauquier C, Soin R, Dierick JF, Gueydan C, Kruys V (June 2010). "The splicing factor ASF/SF2 is associated with ...
Caspase 8
TRAIL-activated apoptotic signaling pathway. • proteolysis. • macrophage differentiation. • TRIF-dependent toll-like receptor ... cysteine-type endopeptidase activity involved in apoptotic process. • tumor necrosis factor receptor binding. • cysteine-type ... Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. ... apoptotic process. • extrinsic apoptotic signaling pathway. • negative regulation of extrinsic apoptotic signaling pathway via ...
STAT5
Activated STAT5 dimers are, however, short-lived and the dimers are made to undergo rapid deactivation. Deactivation may be ... For example, mutations may lead to increased expression of anti-apoptotic genes, the products of which actively prevent cell ... Indirect inhibition targets kinases associated with STAT5, or targets proteases that carry out terminal truncation of proteins ... Cytokine Growth Factor Rev. 10 (2): 131-57. doi:10.1016/S1359-6101(99)00011-8. PMID 10743504. Nosaka T, Kawashima T, Misawa K, ...
Rho-associated protein kinase
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), ... Active ROCK in these cells seems to stimulate the disruption of E-Cadherin-mediated cell-cell contacts by activating actomyosin ... ROCKs contribute to neurite retraction by inducing growth cone collapse by activating actomyosin contractility. It is also ...
Collectin
"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 ... SP-A and SP-D can suppress activated T-lymphocytes and IL-2 (interleukin-2) production. SP-D increases bacterial antigen ...
Biochemical cascade
... of a serine protease and its glycoprotein co-factors are activated to become active components that then catalyze the next ... Recruitment of FAK by integrin leads to Akt activation and this inhibits pro-apoptotic factors like BAD and Bax. When adhesion ... The transcriptional factors are activated by the primary messengers, in most cases, due to their function as nuclear receptors ... FGF (Fibroblast Growth Factor) ligands bind to receptors tyrosine kinase, FGFR (Fibroblast Growth Factor Receptors), and form a ...
Geoffrey M. Cooper
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 ... B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway. ... Mammalian transcription factor LSF is a target of ERK signaling. J. Cell. Biochem. 89:733-746. Hartley, D. and Cooper, G.M. ...
Caspase 8
"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. ... This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like ... Further work revealed that caspase-8 was essential for the induction of the transcription factor "nuclear factor κB" (NF-κB) ...
Caspase 3
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 ... In intrinsic activation, cytochrome c from the mitochondria works in combination with caspase-9, apoptosis-activating factor 1 ... This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10 ...
Myc
... proteins are transcription factors that activate expression of many pro-proliferative genes through binding enhancer box ... In B cells, Myc acts as a classical oncogene by regulating a number of pro-proliferative and anti-apoptotic pathways, this also ... Myc cleavage is mediated by the calpain family of calcium-dependent cytosolic proteases. The cleavage of Myc by calpains is a ... Myc is activated upon various mitogenic signals such as serum stimulation or by Wnt, Shh and EGF (via the MAPK/ERK pathway). By ...
Excitatory synapse
... proteases, and thus the apoptotic cascade. Additional sources of neuronal cell death related to excitotoxicity involve energy ... including activating and inactivating certain K+ channels. Epinephrine is found in the lateral tegmental system, medulla, ... Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, ... ions into the postsynaptic cell through ion channels activated by neurotransmitter binding. There are two different kinds of ...
PSEN1
regulation of epidermal growth factor-activated receptor activity. • regulation of resting membrane potential. • regulation of ... apoptotic process. • activation of MAPKK activity. • thymus development. • positive regulation of coagulation. • negative ... such that they either directly regulate gamma secretase activity or themselves are protease enzymes. Multiple alternatively ... negative regulation of epidermal growth factor-activated receptor activity. • cell adhesion. • hematopoietic progenitor cell ...
NPM1 - Wikipédia, a enciclopédia livre
transcription factor binding. • activating transcription factor binding. • rRNA binding. • protein N-terminus binding. • ... negative regulation of apoptotic process. • regulation of DNA damage response, signal transduction by p53 class mediator. • ... 2008). «Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases.». J Cell ... positive regulation of NF-kappaB transcription factor activity. • protein oligomerization. • negative regulation of protein ...
Proteasome
Due to its role in generating the activated form of NF-κB, an anti-apoptotic and pro-inflammatory regulator of cytokine ... Degradation of Aux/IAA proteins derepresses transcription factors in the auxin-response factor (ARF) family and induces ARF- ... See also: threonine protease § mechanism. The proteasome functions as an endoprotease.[64][65][66][67] The mechanism of ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ...
Beta-amiloide, a enciclopedia libre
... in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis". Gene 488 (1-2 ... funcionando como un factor de transcrición,[12][13] e actividades antimicrobianas (potencialmente asociadas con actividades ... necesítase un composto que poida bloquear o sitio activo das aspartil proteases e que poida atravesar a barreira ... "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science 286 ( ...
Tumor necrosis factor alpha
... which then activates JNK. JNK translocates to the nucleus and activates transcription factors such as c-Jun and ATF2. The JNK ... protease binding. • tumor necrosis factor receptor binding. • cytokine activity. • identical protein binding. ... activation of cysteine-type endopeptidase activity involved in apoptotic process. • tumor necrosis factor-mediated signaling ... TNF, DIF, TNF-alpha, TNFA, TNFSF2, Tumour necrosis factor, TNF-α, tumor necrosis factor, TNLG1F, Tumor necrosis factor alpha. ...
PRNP
negative regulation of activated T cell proliferation. • cellular response to drug. • cell cycle arrest. • learning or memory. ... The protein can exist in multiple isoforms, the normal PrPC and protease-resistant forms designated PrPRes such as the disease- ... negative regulation of apoptotic process. • response to oxidative stress. • negative regulation of sequence-specific DNA ... This can arise from genetic factors, infection from external source, or spontaneously for reasons unknown. Accumulation of PrP ...
Hepatocyte growth factor
... regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling ... negative regulation of apoptotic process. • regulation of branching involved in salivary gland morphogenesis by mesenchymal- ... It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta- ... Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is ...
Lichen planus
Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF ... the release of proinflammatory mediators and proteases by mast cells, and. *perturbations in the innate immune response that ... Liquefaction degeneration of the basal layer with apoptotic keratinocytes (referred to as Civatte, colloid, hyaline, or cytoid ... activates CD8+ T cells on keratinocytes or by encounters with activated CD4+ helper T cells or cytokines produced by activated ...
Caspase
... s (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of ... There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in ... Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. ... Creagh, Emma M. (December 2014). "Caspase crosstalk: integration of apoptotic and innate immune signalling pathways". Trends in ...
GPER
nuclear fragmentation involved in apoptotic nuclear change. • positive regulation of endothelial cell apoptotic process. • ... adenylate cyclase-activating G-protein coupled receptor signaling pathway. • modulation of chemical synaptic transmission. ... cellular response to tumor necrosis factor. • cellular response to estradiol stimulus. • cellular response to peptide hormone ... apoptotic process. • positive regulation of cAMP biosynthetic process. • negative regulation of fat cell differentiation. • ...
Integrin beta 3
protease binding. • platelet-derived growth factor receptor binding. • GO:0001948 protein binding. • identical protein binding ... apoptotic cell clearance. • regulation of postsynaptic neurotransmitter receptor internalization. • regulation of protein ... "The phosphotyrosine binding-like domain of talin activates integrins". J. Biol. Chem. 277 (24): 21749-58. doi:10.1074/jbc. ... fibroblast growth factor binding. • insulin-like growth factor I binding. • C-X3-C chemokine binding. • integrin binding. • ...
Caspase
Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of ... There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in ... Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. ...
GDF11
transforming growth factor beta receptor binding. • growth factor activity. • GO:0001948 protein binding. ... regulation of apoptotic process. • skeletal system development. • palate development. • ureteric bud development. • regulation ... GDF11 also activates the Smad2/3 phosphorylation pathway in skin endothelial cells and improves skin vasculature.[17] ... protease inhibitor, and NTR domains.[43] WFIKKN2 has a high affinity for GDF11, and previously has been found to inhibit the ...
Phagosome
... due to a lower concentration of lysosomal proteases and even the presence of protease inhibitors. ... Listeriolysin is activated by the acidic environment of the phagosome.[33] In addition, Listeria secrete two phospholipase C ... Pathogen-infected apoptotic cells will trigger inflammation, but damaged cells that are degraded as part of the normal tissue ... which is hypothesised to prevent membrane recycling and recruitment of fusion factors, so the phagosome does not fuse with ...
HIV associated cardiomyopathy
Protease inhibitors are another group of drugs (e.g. ritonavir) and some of them can cause a range of problems such as: ... Cellular basis for the negative inotropic effect of tumor necrosis factor alpha in the adult mammalian heart. J Clin Invest ... and cytokine apoptotic signaling. Cardiovasc Toxicol 2004;4:97-107. Twu C, Liu QN, Popik W, et al. Cardiomyocytes undergo ... Alternatively, the immunoglobulins can reduce the effects or secretions of cytokines and cellular growth factors. Signs and ...
Neutrophil
Once activated, they change shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens. ... Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase ... "Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes". Infect. Immun. 79 (11): ... "ITAM signaling by Vav family Rho guanine nucleotide exchange factors regulates interstitial transit rates of neutrophils in ...
Wound healing
Phagocytes further release proteases that break down the ECM of neighbouring tissue, freeing the activated fibroblasts to ... Overview of involved growth factorsEdit. Following are the main growth factors involved in wound healing: Growth factor. ... in addition to their role in host defense and in the clearance of apoptotic cells, are being increasingly recognized for their ... Factors affecting wound healingEdit. Many factors controlling the efficacy, speed, and manner of wound healing fall under two ...
Cell nucleus
The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin ... and eventually activating the transcription factor NF-κB. A nuclear localisation signal on the NF-κB protein allows it to be ... There they serve as transcription factors when bound to their ligand; in the absence of a ligand, many such receptors function ... Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity.[15] ...
Retinoblastoma protein
transcription factor binding. • RNA polymerase II activating transcription factor binding. • phosphoprotein binding. • kinase ... hepatocyte apoptotic process. • apoptotic process. • positive regulation of transcription regulatory region DNA binding. • ... Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the ... transcription factor complex. • spindle. • cyclin/CDK positive transcription elongation factor complex. • chromatin. • cell ...
Philadelphia chromosome
The JAK/STAT pathway moderates many of these effectors by activating STATs, which are transcription factors with the ability to ... The function of these pro-apoptotic proteins, however, is impaired, and apoptosis is not carried out in these cells. BCR-ABL ... have also been identified in downregulating BCR-ABL kinase translation and promoting its degradation by protease.[23][24] ... BCR-ABL fusion cells also exhibit constitutively high levels of activated Ras bound to GTP, activating a Ras-dependent ...
TNFRSF10A - Википедия
extrinsic apoptotic signaling pathway via death domain receptors. • TRAIL-activated apoptotic signaling pathway. • cellular ... protease binding. • receptor activity. • death receptor activity. • protein binding. • transcription factor binding. ... Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a (неопр.). *↑ Miyazaki, T; Reed J C. A GTP-binding ... apoptotic process. • signal transduction. • activation of NF-kappaB-inducing kinase activity. • ...
MALT1
protease binding. • protein self-association. • peptidase activity. • protein binding. • kinase activator activity. • cysteine- ... regulation of apoptotic process. • defense response. • regulation of T cell receptor signaling pathway. • negative regulation ... It has an important role in the activation of the transcription factor NF-κB, in the production of interleukin-2 (IL-2) and in ... Cells expressing an uncleavable A20 mutant is however still capable to activate NF-κB, but cells expressing the C-terminal or ...
Neurotensin receptor 1
negative regulation of apoptotic process. • positive regulation of release of sequestered calcium ion into cytosol. • D- ... accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated ... Growth factor. See here instead.. Insulin. *Agonists: Chaetochromin (4548-G05). *Insulin-like growth factor 1 ... positive regulation of apoptotic process. • negative regulation of release of sequestered calcium ion into cytosol. • positive ...
Mdm2
In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. ... peroxisome proliferator activated receptor binding. • ubiquitin binding. Cellular component. • cytosol. • endocytic vesicle ... negative regulation of apoptotic process. • cellular response to organic substance. • cellular response to hydrogen peroxide. • ... Mdm2 also interacts with a ubiquitin specific protease, USP7, which can reverse Mdm2-ubiquitylation and prevent it from being ...
Apaf1 - Apoptotic protease-activating factor 1 - Mus musculus (Mouse) - Apaf1 gene & protein
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the ... 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 ... IPR017251. Apaf-1. IPR037963. APAF1_CARD_dom. IPR024977. Apc4_WD40_dom. IPR001315. CARD. IPR011029. DEATH-like_dom_sf. ...
Requirement of Apoptotic Protease-Activating Factor-1 for Bortezomib-Induced Apoptosis but Not for Fas-Mediated Apoptosis in...
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 ... 2005) Plasma membrane sequestration of apoptotic protease-activating factor-1 in human B-lymphoma cells: a novel mechanism of ...
Apoptotic protease-activating factor 1
positive regulation of apoptotic signaling pathway 23 intrinsic apoptotic signaling pathway in response to endoplasmic ... The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates ... cellular response to transforming growth factor beta stimulus 54 activation of cysteine-type endopeptidase activity involved in ... activation of cysteine-type endopeptidase activity involved in apoptotic process 80 ...
Apoptotic protease-activating factor 1 (Apaf-1) as a liable gene for spontaneous mutations in vitro
The apoptotic protease-activating factor 1 (Apaf-1) receives the death signal in the intrinsic ormitochondrial pathway of ... Upon the releasing of cytochrome c from theintermembrane space of mitochondria and binding to Apaf-1 molecules, a ... Here, for thefirst time we present spontaneous mutations and recombinations of the Apaf-1 gene and itsneighbouring sequences. ... incubation temperatures and the number of unwanted spontaneous mutations.During our experiment we found that the Apaf-1 gene is ...
Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? | Cell Death & Disease
... tumour necrosis factor-related apoptosis-inducing agent. Together, we also will have a look from clinical perspective to ... Owing to the fact that apoptosis causes minimal inflammation and damage to the tissue, apoptotic cell death-based therapy has ... apoptotic protease activating factor 1; FADD, Fas-associated death domain; TRADD, TNFR-associated death domain protein ... the key constituent of apoptosome called apoptotic protease activating factor 1 binds procaspase 9 via interface with its ...
Mitochondrial-Shaping Proteins in Cardiac Health and Disease - the Long and the Short of It! | SpringerLink
BAK and Apoptotic protease activating factor 1 (APAF1) to amplify cell death caused by certain factors such as BID and ... cytosolic calcium overload which occurs during acute IRI may activate calcineurin thereby dephosphorylating and activating Drp1 ... as well as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha ... The apoptotic protein tBid promotes leakage by altering membrane curvature. J Biol Chem. 2002;277:32632-9.PubMedCrossRefGoogle ...
p53- and Bax-Mediated Apoptosis in Injured Rat Spinal Cord | SpringerLink
Apoptotic protease activating factor 1. ATM. Ataxia telangiectasia mutated. ATR. Ataxia telangiectasia and Rad3 related ... Expression of APAF1, caspase 9 and caspase 3 activities confirmed the intrinsic apoptotic pathway after SCI. Activated p53 and ... Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res ... Eve DJ, Dennis JS, Citron BA (2007) Transcription factor p53 in degenerating spinal cords. Brain Res 1150:174-181PubMedCrossRef ...
Apoptotic protease activating factor 1 inducing apoptosis and related anti-tumor therapy -- review | Journal of Experimental...
Apoptosis , Apoptotic Protease-Activating Factor 1 , Metabolism , Caspase 9 , Metabolism , Humans , Neoplasms , Therapeutics , ... Apoptotic protease activating factor 1 inducing apoptosis and related anti-tumor therapy -- review / 中国实验血液学杂志 ... Apoptotic protease activating factor-1 (Apaf1) is an essential factor in intrinsic mitochondrial pathway of apoptosis ... Apoptotic protease activating factor 1 inducing apoptosis and related anti-tumor therapy - ...
Negative regulation of the Apaf-1 apoptosome by Hsp70
Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its ... Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1- ... Apoptotic Protease-Activating Factor 1 * Cell Extracts * Cytochrome c Group * Deoxyadenine Nucleotides ... Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its ...
Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action
Apoptotic protease activating factor 1. APC:. Activated protein C. Bax:. Bcl-2-associated X protein. ... EGFR: epidermal growth factor receptor, TGFβ R1/2: transforming growth factor, beta receptor 1/2, EMT: epithelial-mesenchymal ... Transforming growth factor-β (TGF-β) is a multifunctional polypeptide that binds to specific TGF-β receptors for paracrine and ... Caffeic acid showed apoptotic cell death against HCT 15 cell lines although IC50 value was very high (800 μM). Similar findings ...
RCSB PDB - 5JUY: Active human apoptosome with procaspase-9
Apoptotic protease-activating factor 1. A, B, C, D, E, F, G. 1248. Homo sapiens. Mutation(s): 0 Gene Names: APAF1, KIAA0413. ... On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, ... This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. ... In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near ...
Autophagic and Apoptotic Effects of HDAC Inhibitors on Cancer Cells
Apoptotic protease-activating factor 1. Atg:. Autophagy-related gene. BAPTA:. 1,2-bis(o-aminophenoxy)ethane-N,N,. -tetraacetic ... In both pathways, activated caspases (cysteine aspartic acid-specific proteases) cleave their substrates and activate other ... the p53 tumor-suppressor protein is stabilized and activated as a transcription factor, capable of inducing apoptosis. Nuclear ... At that time, ERK was specifically activated at a lower concentration but not at a higher concentration of retinamide [57].(11) ...
Molecules | Free Full-Text | Astaxanthin Protects PC12 Cells against Homocysteine- and Glutamate-Induced Neurotoxicity | HTML
... 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). ... Figure 7. Summary of the apoptotic pathways induced by ... Chang, C.H.; Chen, C.Y.; Chiou, J.Y.; Peng, R.Y.; Peng, C.H. Astaxanthine secured apoptotic death of PC12 cells induced by beta ...
A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia
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 ...
APAF1 peptide (ab7873) | Abcam
Apoptotic protease activating factor. *Apoptotic protease activating factor 1. *Apoptotic protease-activating factor 1 ... Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the ... Contains 1 CARD domain.. Contains 1 NB-ARC domain.. Contains 13 WD repeats. ... Apoptotic peptidase activating factor 1. * ...
Anti-Caspase-9 antibody [10-1-87] (ab115792) | Abcam
10-1-87] validated for WB and tested in Human. Immunogen corresponding to recombinant full length protein ... Apoptotic protease Mch-6 antibody. *Apoptotic protease-activating factor 3 antibody. *CASP-9 antibody ... All lanes : Anti-Caspase-9 antibody [10-1-87] (ab115792) at 1 µg/ml. Lane 1 : Jurkat cell lysate. Lane 2 : Jurkat cell lysate, ... Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Proteolytically ...
Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors | PNAS
2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature 434:926-933. ... 2F). Hence, recognition of one or more MAMPs expressed by Pto DC3000ΔhrpL activates MTI responses that result in SA ... Hence, ADR1-L2 is not activated via the canonical mechanism used by NB-LRR and NLR receptors as microbial sensors, at least for ... STAND proteins are molecular switches that toggle from an ADP-bound "off" position to an ATP-bound "on" state that activates ...
IJERPH | Free Full-Text | Cellular and Mitochondrial Effects of Alcohol Consumption | HTML
Apoptotic protease activating factor-1; ATP, adenosine triphosphate; ADP, adenosine diphosphate. ... Apoptotic protease activating factor-1; ATP, adenosine triphosphate; ADP, adenosine diphosphate. ... favoring the translocation to the mitochondria of the pro-apoptotic factor Bax that forms a complex with a voltage-dependent ... favoring the translocation of the pro-apoptotic factor bax, which forms a complex with voltage-dependent anion channel (VDAV). ...
Growth Factor Signaling in Cell Survival: Implications for Cancer Treatment | Journal of Pharmacology and Experimental...
Once in the cytoplasm, cytochrome c binds to apoptotic protease-activating factor-1, which binds and activates caspase-9 ... apoptotic protease-activating factor 1; PKA, cAMP-dependent protein kinase; ANT, adenine nucleotide transporter. ... nerve growth factor), brain-derived neurotrophic factor, and growth factors (insulin-like growth factor-1, platelet-derived ... Protection from growth factor withdrawal-induced cell death through enforced expression of anti-apoptotic Bcl-2 family members ...
Expression of APAF1 in cancer - Summary - The Human Protein Atlas
APAF-1, CED4) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers. ... Apoptotic protease-activating factor 1 Show all. Predicted intracellular proteins. Plasma proteins. Cancer-related genes. ... Apoptotic peptidase activating factor 1. Protein classi. Protein class the gene product belongs to according to selected gene ... Apoptotic peptidase activating factor 1 (HGNC Symbol). Entrez gene summary. This gene encodes a cytoplasmic protein that ...
Luteolin inhibits multi-heavy metal mixture-induced HL7702 cell apoptosis through downregulation of ROS-activated mitochondrial...
2772), apoptotic protease activating factor 1 (Apaf1; cat. no. 8969), cleaved caspase-9 (cat. no. 7237), caspase-3 (cat. no. ... Apoptotic analysis. Multi-heavy metal mixture induced HL7702 cell apoptosis in a dose-dependent manner, while 20 μM luteolin ... Apoptotic assays revealed that the multi-heavy metal mixture induced HL7702 cell apoptosis in a dose-dependent manner, which ... Certain harmful extracellular factors may break this balance, resulting in excessive ROS generation beyond the cell scavenging ...
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. - PubMed - NCBI
Apoptotic Protease-Activating Factor 1. *Cytochrome c Group. *Deoxyadenine Nucleotides. *Multienzyme Complexes ... Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 ... indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and ... We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 ...
Harte MT[au] - PubMed - NCBI
Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the WD-40 repeat region. ... Mutations within subdomain II of the extracellular region of epidermal growth factor receptor selectively alter TGF alpha ... 2016 Oct 5;109(1). doi: 10.1093/jnci/djw199. Print 2017 Jan. ... 1.. Activation of STING-Dependent Innate Immune Signaling By S- ...
Cytochrome c - Wikipedia
Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1).[5] ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 ... Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... intrinsic apoptotic signaling pathway. • activation of cysteine-type endopeptidase activity involved in apoptotic process by ...
Programmed cell death - Wikipedia
Knockout or inhibition of apoptotic protease activating factor 1 (APAF1), also results in malformations and increased embryonic ... An atrophic factor is a force that causes a cell to die. Only natural forces on the cell are considered to be atrophic factors ... Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ... Solomon M, Belenghi B, Delledonne M, Menachem E, Levine A (1999). "The involvement of cysteine proteases and protease inhibitor ...
Picornaviruses and Apoptosis: Subversion of Cell Death | mBio
... apoptotic protease activating factor 1.. TOLL-LIKE RECEPTORS IN APOPTOSIS. Toll-like receptors (TLRs) are specialized, cellular ... where it complexes with apoptotic peptidase-activating factor 1 (APAF-1) [Fig. 1(x)] and recruits procaspase-9, inducing ... The major apoptotic pathway activated and suppressed by poliovirus. J Virol77:45-56. doi:10.1128/JVI.77.1.45-56.2003. ... The Picornavirus proteases are not only essential for cleavage of viral polyprotein but they also target cellular factors to ...
Caspase-9 (ICE like apoptotic protease 6, Apoptotic protease Mch-6, Apoptotic protease activating factor 3) | BioVendor
Apoptotic protease Mch-6, Apoptotic protease activating factor 3) Caspase-9 (ICE like apoptotic protease 6, Apoptotic protease ... Apoptotic protease activating factor 3). Caspases are the executioners of apoptosis. This cysteine protease family consists of ... Activated caspase-9 in turn cleaves and activates caspase-3; caspase-9 thus is the most upstream member of the apoptotic ... You are here: Home Products by Molecule of Interest Caspase-9 (ICE like apoptotic protease 6, ...
Anti-Mouse (Murine) APAF1 antibody for Immunohistochemistry (Paraffin-embedded Sections) (IHC (p))
Apoptotic protease-activating factor 1, KIAA0413 Gene ID 317 NCBI Accession NP_001151 ... 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 ... Images for product: anti-Apoptotic Peptidase Activating Factor 1 (APAF1) (N-Term) antibody ...
anti-APAF1 antibody (Apoptotic Peptidase Activating Factor 1) (AA 12-28)</span...
... for Apoptosis Protease Activating Factor-1). Cytochrome c associates with APAF-1 in the presence of dATP or ATP and induces an ... anti-APAF1 antibody (Apoptotic Peptidase Activating Factor 1) (AA 12-28) APAF1 antibody (Apoptotic Peptidase Activating Factor ... Apoptotic Peptidase Activating Factor 1 (APAF1) show synonyms for this antigen * APAF1 ... anti-Apoptotic Peptidase Activating Factor 1 (APAF1) (AA 12-28) antibody (Image 2) Read product details ...
Polarized Scorpion Venom Solution and a Method for Making Polarized Scorpion Venom Solution - Mikaelian, Arthur
... "apoptotic protease activating factor-1"). Using the energy provided by ATP, these complexes aggregate to form apoptosomes. The ... Some examples of positive signals: growth factors for neurons; and Interleukin-2 (IL-2), an essential factor for the mitosis of ... Cell survival is maintained by a balance between pro-apoptotic and anti-apoptotic stimuli. Dysregulation of apoptosis can ... They are all proteases. They get their name because they cleave proteins, mostly each other, at aspartic acid (Asp) residues. ...
Apaf1Signaling pathwayCaspasesProteinsPathwaysApoptosomeIntrinsic apoptoticMitochondriaCleavesTumorSignalsCysteine proteaseMetabolismExtrinsicStimuliKinaseEffectorActivationCleavageCytosolNeuronsCytochrome c releaseCascadeSerineOligomerizationCellularCell deathGeneRegulationReceptorMoleculesReceptorsInhibitorTranscriptionAntibodyMitochondrial membraneFamilyDownregulation2018IntracellularGenes
Apaf110
- Expression of APAF1, caspase 9 and caspase 3 activities confirmed the intrinsic apoptotic pathway after SCI. (springer.com)
- Apoptotic protease activating factor-1 (Apaf1) is an essential factor in intrinsic mitochondrial pathway of apoptosis activation. (bvsalud.org)
- Apaf1 leads to the formation of apoptosome , which then proteolytically activates caspase-9 . (bvsalud.org)
- Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene. (wikipedia.org)
- APAF1 has been shown to interact with: APIP, BCL2-like 1 Caspase-9, HSPA4, and NLRP1. (wikipedia.org)
- NOD proteins include the apoptosis regulator APAF1 (apoptotic protease activating factor 1) and mammalian NOD-LRR proteins. (novusbio.com)
- The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. (biologists.org)
- This function of Apaf1 is carried out during the cell life and is not related to its apoptotic role. (biologists.org)
- The apoptotic protease activating factor 1 (Apaf1) is one of the most studied proapoptotic proteins. (biologists.org)
- Cytochrome c is then released from mitochondria to activate adapter protein apoptotic protease-activating factor-1 (APAF1), which forms the apoptosome with dimerized initiator caspase 9. (biolegend.com)
Signaling pathway3
- In this paper , the structure and function of Apaf-1, the mechanism involved in Apaf-1 signaling pathway, and application of Apaf-1 in tumor therapy were reviewed. (bvsalud.org)
- Apoptosis (programmed cell death), triggers an extrinsic (death receptor-mediated signaling) or an intrinsic (mitochondria-mediated signaling) pathway to activate caspase-3, leading to morphological alterations (e.g. (spandidos-publications.com)
- The dualistic role of the retinoic acid signaling pathway in cancer is revealed in its gene transcription targets, cross-talk with other transcription factors, mediation of apoptotic pathways, and influence in the immune system. (omicsonline.org)
Caspases33
- Upon the releasing of cytochrome c from the intermembrane space of mitochondria and binding to Apaf-1 molecules, a heptameric apoptosome complex is formed and triggers the downstream cascade of caspases. (ac.ir)
- The activated caspase-9 opens the downstream signal of caspases to execute programmed cell death . (bvsalud.org)
- and (5) activating cascade of caspases involving caspases 12 and 3. (mdpi.com)
- For dying cells to adopt these features, the activation of a family of cysteine proteases, termed caspases, is required. (aspetjournals.org)
- This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. (spandidos-publications.com)
- The direct cleavage of caspases ( 2 ), disruption of nuclear-cytoplasmic trafficking ( 3 , 4 ), relocalization of proapoptotic proteins ( 5 , 6 ), and cleavage of essential apoptotic adaptor proteins ( 7 , 8 ) have all been shown to occur as a result of action of Picornavirus protease activity and together suggest mechanisms by which picornaviruses can alter host cell apoptotic death pathways. (asm.org)
- These pro-apototic factors in turn activate initiator and executer caspases. (biologists.org)
- During apoptosis, this motif is cleaved by caspases, causing the release of cytochrome c into the cytosol, which then further promotes caspase activity and, by extension, becomes pro-apoptotic. (thermofisher.com)
- This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC.A third apoptotic caspase, DRICE, is activated throughout the length of individualizing spermatids in a process that requires the product of the driceless locus, which also participates in individualization.Our results demonstrate that multiple caspases and caspase regulators, likely acting at distinct points in time and space, are required for spermatid individualization, a nonapoptotic process. (nih.gov)
- This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC. (nih.gov)
- This antibody will be useful in studies of the activation of caspases through Apaf-1 and also in metastatic melanomas where Apaf-1 is inactivated which leads to defects in the execution of apoptotic cell death. (creative-biogene.com)
- The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the main executioners of apoptosis. (ebi.ac.uk)
- As caspase-9 cleaves proteins, it activates other caspases from its family. (wikibooks.org)
- This apoptosome then activates a cascade of cellular destruction events, beginning with the activation of death-execution effector caspases, such as caspase 3, followed by the activation of downstream caspases, ultimately resulting in the hallmark of apoptosis including condensation of nuclear and cytoplasmic contents, fragmentation of nuclear DNA, and membrane blebbing. (spiedigitallibrary.org)
- Activated caspases induce apoptosis. (ersjournals.com)
- Similarly to caspase-8, active caspase-9 then proteolytically activates downstream effector caspases, which by degrading various cellular proteins propagate the apoptotic signal. (bloodjournal.org)
- Recruitment of procaspase-9 to the apoptosome results in its activation, allowing it to cleave and activate executioner caspases, such as caspase-3, which orchestrate the destruction of the cell ( Boatright and Salvesen, 2003 ). (rupress.org)
- Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1-associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. (aacrjournals.org)
- In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (rupress.org)
- Caspases lead to the proteolysis of a number of cellular substrates, a process which finally results in the apoptotic collapse of the cell. (rupress.org)
- Caspases are present as inactive zymogens that are activated during apoptosis ( 6 ). (aacrjournals.org)
- Initiators such as caspase-8 and caspase-9 are apical caspases that are activated on binding to specialized molecular platforms that are assembled through selective protein-protein interactions. (aacrjournals.org)
- Activated initiator caspases can then cleave and activate effector caspases, such as caspase-3 and caspase-7, through trans-proteolytic processing ( 12 ). (aacrjournals.org)
- Caspases, a family of cysteine acid proteases, are central regulators of apoptosis. (cellsignal.com)
- Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7), which in turn cleave cytoskeletal and nuclear proteins like PARP, α-fodrin, DFF and lamin A, and induce apoptosis. (cellsignal.com)
- Fas and TNFR activate caspases 8 and 10 (2), DNA damage leads to the activation of caspase-9 and ER stress leads to the calcium-mediated activation of caspase-12 (3). (cellsignal.com)
- [7] Both pathways induce cell death by activating caspases , which are proteases , or enzymes that degrade proteins. (wikipedia.org)
- The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately. (wikipedia.org)
- Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis. (wikipedia.org)
- This process is regulated by proteases called caspases, as well as signaling proteins from the Bcl-2 family. (biolegend.com)
- Initiator caspases are activated by dimerization, which is driven by several pathways described below. (biolegend.com)
- Dimerized initiator caspases will cleave and activate executioner caspases. (biolegend.com)
- Granzyme B can directly cleave and activate initiator and executioner caspases. (biolegend.com)
Proteins37
- In this review, we reconnoitre the two major pathways (intrinsic and extrinsic) targeted cancer therapeutics, steering toward chief modulators of these pathways, such as B-cell lymphoma 2 protein family members (pro- and antiapoptotic), inhibitor of apoptosis proteins, and the foremost thespian of extrinsic pathway regulator, tumour necrosis factor-related apoptosis-inducing agent. (nature.com)
- By undergoing fission they generate fragmented discrete mitochondria, a process which is regulated by the mitochondrial fission proteins, dynamic-related peptide-1 (Drp1), human fission protein-1 (hFis1), mitochondrial fission factor (Mff) and mitochondrial dynamics proteins 49 and 51 (MiD49 and 51). (springer.com)
- Plant NB-LRR proteins belong to the STAND (signal transduction ATPases with numerous domains) superfamily, which includes the animal apoptotic proteins Apaf-1/CED4 and innate immune receptors of the nucleotide-binding domain and leucine-rich repeat-containing proteins (NLR) family ( 5 ). (pnas.org)
- STAND proteins are molecular switches that toggle from an ADP-bound "off" position to an ATP-bound "on" state that activates downstream signaling. (pnas.org)
- Receptor engagement then leads to the recruitment of death domain (DD) containing proteins as the Fas-associated DD, which serve to bind and activate caspase-8 that in turn ultimately initiates a cascade of caspase activation (Fig. 1 ). (aspetjournals.org)
- Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). (spandidos-publications.com)
- These proteases are essential for viral polyprotein processing and also cleave cellular proteins. (asm.org)
- Picornavirus proteases cleave proapoptotic adaptor proteins, resulting in downregulation of apoptosis. (asm.org)
- The single open reading frame of the genome is translated into a large polyprotein that undergoes posttranslational processing ( cis and trans cleavage) by the virally encoded proteases to yield mature, structural or nonstructural proteins ( 14 ). (asm.org)
- The viral proteases not only participate in the maturation of the viral proteins but also act against cellular factors, resulting in host cell shutoff and increased virus replication. (asm.org)
- Many apoptotic cell deaths in Drosophila utilize the REAPER/HID/GRIM family proapoptotic proteins. (nih.gov)
- These proteins promote cell death, at least in part, by disrupting interactions between the caspase inhibitor DIAP1 and the apical caspase DRONC, which is continually activated in many viable cells through interactions with ARK, the Drosophila homolog of the mammalian death-activating adaptor APAF-1. (nih.gov)
- Proteins containing this domain include the low affinity neurotrophin receptor p73, Fas, FADD (Fas-associated death domain protein), TNF-1 (tumour necrosis factor receptor-1), Pelle protein kinase, and the Tube adaptor protein [ PMID: 15226512 ]. (ebi.ac.uk)
- Proteins containing CARD include Raidd, APAF-1 (apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation). (ebi.ac.uk)
- Inhibitors of apoptosis proteins X-chromosome-linked inhibitor of apoptosis, cellular inhibitor of apoptosis protein-1, and survivin were significantly down-regulated in TK6 cells, but not in WTK1 cells. (aacrjournals.org)
- Mechanisms that may contribute to lower satellite cell proliferation and differentiation in muscles of the OZR could include decreases in the expression levels of myogenic regulatory factor proteins. (physiology.org)
- Activated neutrophils release extracellular traps (neutrophil extracellular traps, NETs), an extracellular matrix composed of nuclear and mitochondrial DNA armed with granular proteins, cell-specific proteases, and antimicrobial peptides ( 10 , 11 ). (pnas.org)
- Caspase-9 is a protease that cleaves proteins. (wikibooks.org)
- Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two proapoptotic Bcl-2 proteins, Bad and Bax, were examined in β-cells. (diabetesjournals.org)
- Multidomain proapoptotic proteins, such as Bax and Bak, contain the conserved Bcl-2 homology (BH) domains 1-3. (diabetesjournals.org)
- We found that ADEVs released in response to IL-1β (ADEV-IL-1β) and TNFα (ADEV-TNFα) were enriched with miRNAs that target proteins involved in neurotrophin signaling. (nature.com)
- In this Review, we discuss how a pro-apoptotic subgroup of the BCL2 protein family, known as the BH3-only proteins, controls apoptosis and anoikis during mammary gland homeostasis and to what extent their inhibition confers tumor suppressive functions in metastatic breast cancer. (biologists.org)
- Specifically, the role of the two pro-apoptotic BH3-only proteins BCL2-modifying factor (BMF) and BCL2-interacting mediator of cell death (BIM) will be discussed here. (biologists.org)
- We assess current developments in treatment that focus on mimicking the function of the BH3-only proteins to induce apoptosis, and consider their applicability to restore normal apoptotic responses in anchorage-independent disseminating tumor cells. (biologists.org)
- These stimulated kinases directly or indirectly activate phosphorylation of proteins from apoptotic pathways: tumor suppressor p53 , breast and ovarian cancer susceptibility protein 1 ( Brca1 ), E2F transcription factor 1 ( E2F1 ), proto-oncogene tyrosine-protein kinase c-Abl and cell cycle regulator RAD9 . (bio-rad.com)
- 6 ] Moreover, JNK stimulates activity of proapoptotic proteins, Bcl-2 modifying factor ( BMF ) and BCL2-like 11 factor ( Bim ). (bio-rad.com)
- Other proteins released from the intermembrane space of mitochondria are the Apoptosis Inducing Factor (AIF), Smac/Diablo and Omi. (rsc.org)
- Members of the Bcl-2 family are pivotal regulators of the apoptotic process ( Antonsson and Martinou, 2000 ) and include both proteins that promote cell survival (e.g. (jneurosci.org)
- The effects of [beta]-sitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. (thefreelibrary.com)
- Structural, Biochemical and Functional Analyses of CED-9 Recognition by the Pro-apoptotic Proteins EGL-1 and CED-4. (tsinghua.edu.cn)
- Myeloid cell leukemia type 1 (Mcl-1) is one of the antiapoptotic Bcl-2 family proteins. (intechopen.com)
- These movements result from competitive microtubule polymerization and depolymerization or through the actions of microtubule motor proteins (1). (cellsignal.com)
- To reach their native conformation, many secretory proteins require the formation of intra- or inter-molecular disulfide bonds (1). (cellsignal.com)
- The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. (aacrjournals.org)
- The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. (aacrjournals.org)
- Background: Caspase-3 (CPP-32, Apoptain, Yama, SCA-1) is a critical executioner of apoptosis, as it is either partially or totally responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (1). (cellsignal.com)
- Binding of a ligand to its respective receptor activates adaptor proteins that contain death domains, such as FADD and TRADD. (biolegend.com)
Pathways29
- For instance, DNA damage instigated in a cell can leave it with two choices, either to repair that damage or to instruct it to commit suicide through apoptotic pathways because the damage is irreparable. (nature.com)
- Numerous studies have implicated a variety of intracellular signaling pathways, including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and Jak/signal transducers and activators of transcription, as effectors of these extracellular trophic factors. (aspetjournals.org)
- Binding of growth factors to their respective receptors results in the activation of individual and combined pathways resulting in pleiotropic effects on cellular biochemistry. (aspetjournals.org)
- Despite a wide array of distinct trophic factors and receptors that govern the survival of specific cells, many of these receptors use common intracellular signaling molecules and pathways to mediate their signals. (aspetjournals.org)
- Three pathways that have taken center stage in survival signaling are the phosphatidylinositol 3-kinase (PI3K)/Akt, the Ras/mitogen-activated protein kinase, and the Jak/signal transducers and activators of transcription (STAT) pathways. (aspetjournals.org)
- These pathways have been shown to mediate survival signals in several cell types and model organisms and in response to a diverse array of growth factors. (aspetjournals.org)
- This review will present an overview of our current understanding of programmed cell death, also referred to as apoptosis, focusing on growth factor signaling pathways in the context of cell survival and the role of these pathways in carcinogenesis. (aspetjournals.org)
- Picornavirus proteases also cleave nucleoporins, disrupting the orchestrated manner in which signaling pathways use active nucleocytoplasmic trafficking, including those involved in apoptosis. (asm.org)
- Picornaviruses can selectively alter cellular pathways in order to promote viral replication, mostly through the action of viral proteases, including modulation of proapoptotic factors or processes. (asm.org)
- In this minireview, we aim to review and discuss current literature on Picornavirus modulation of cell death pathways with a view to integrating diverse studies to form a rational informed model of Picornavirus disruption of apoptotic pathways. (asm.org)
- The extrinsic and intrinsic apoptosis pathways converge to cleave and activate procaspase-3 to derive caspase 3, which is termed an executioner caspase. (asm.org)
- How is activation of mitochondria-based pathways for the signaling of apoptotic and necrotic cell death avoided under conditions of hypoxia, anoxia, diapause, estivation and anhydrobiosis? (biologists.org)
- Here we report characterization of apoptotic signaling pathways activated by NO · in these cells by cDNA microarray expression and immunoblotting. (aacrjournals.org)
- NO · also modulated levels of several gene products in the mitochondria-dependent and death-receptor-mediated apoptotic pathways. (aacrjournals.org)
- Collectively, these data show that NO · exposure activated a complex network of responses leading to p53-dependent apoptosis via both mitochondrial and Fas receptor pathways, which were abrogated in the presence of mutant p53. (aacrjournals.org)
- While several signaling pathways have been suggested to play a role in cytokine-mediated cell death ( 1 ), it remains unclear how these pathways cooperate to induce apoptosis in β-cells. (diabetesjournals.org)
- The caspase cascade can be activated by different pathways (fig. 1 ⇓ ) 5 . (ersjournals.com)
- Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. (thefreelibrary.com)
- Direct DNA damage by ionizing radiation or UV can activates the interconnected apoptotic pathways by stimulation of protein kinases from phosphoinositide-3-kinases family. (bio-rad.com)
- Activated c-Alb participates in apoptotic pathways (e.g. via phosphorylation tumor p53-related protein ( p73 ) [ 8 ], transcription factor c-Jun or apoptosis-related cysteine protease 9 ( Caspase-9 ). (bio-rad.com)
- E2F may activate apoptosis pathways by stimulation of p53 14-3-3 protein, type tau ( 14-3-3 tau ) is required for expression and induction of E2F1 apoptotic targets, such as p73 , Apaf-1 , and apoptosis-related cysteine protease 3 ( Caspase-3 ). (bio-rad.com)
- Apoptotic pathways of cell death. (cdc.gov)
- Stimulation of apoptosis is responsible for the elimination of potentially harmful or premalignant cells, whereas suppression of apoptotic pathways can lead to uncontrolled cell proliferation and formation of malignancies. (rsc.org)
- Here, we review various signals emitted by distressed or dysfunctional mitochondria and the stress-responsive pathways activated in response to these signals in order to restore mitochondrial function and promote cellular survival. (frontiersin.org)
- The induction of apoptotic pathways in cancer cells offers a novel and potentially useful approach to improve patient responses to conventional chemotherapy. (aacrjournals.org)
- Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. (aacrjournals.org)
- However, little is known about the role of TFPI-2 in the induction of apoptotic pathways in glioblastomas. (aacrjournals.org)
- It has dual functions at the molecular level: Lipin 1 serves as a transcriptional coactivator in liver, and a phosphatidate phosphatase in triglyceride and phospholipid biosynthesis pathways (5). (cellsignal.com)
- Lipin 1 is regulated by mTOR, illustrating a connection between adipocyte development and nutrient-sensing pathways (6). (cellsignal.com)
Apoptosome12
- The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. (nih.gov)
- Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. (nih.gov)
- Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the caspase-recruitment domain (CARD) of Apaf-1 and through inhibition of apoptosome formation. (nih.gov)
- In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). (rcsb.org)
- On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. (rcsb.org)
- Cytochrome c/Apaf-1/caspase-9 form a socalled apoptosome, amplifying the caspase cascade. (biovendor.com)
- By comparing the off state with a recent cryo-electron microscopy derived model of Apaf-1 in its apoptosomal conformation, we depict the molecular events that transform Apaf-1 from autoinhibited monomer to a building block of the caspase-activating apoptosome. (rcsb.org)
- Released cytochrome c interacts with apoptotic protease-activating factor 1, ATP, and pro-caspase 9 to form the apoptosome. (spiedigitallibrary.org)
- It is the core of the apoptosome, which is formed upon triggering of the mitochondrial apoptotic pathway. (biologists.org)
- The complex of procaspase-9, cytochrome c, and Apaf-1 is known as the apoptosome. (bloodjournal.org)
- Once in the cytosol, cytochrome c binds to Apaf-1 to form the apoptosome complex. (rupress.org)
- In the intrinsic pathway, several adverse factors act upon mitochondria to cause loss of the mitochondrial membrane potential, resulting in leakage into the cytosol of cytochrome C (Cyto C), which together with apoptotic protease activating factor 1 forms the apoptosome that activates caspase-9. (cdc.gov)
Intrinsic apoptotic2
- Signals activating the "intrinsic apoptotic pathway" converge on the mitochondria, leading to mitochondrial membrane permeabilization and subsequent release of cytochrome c from the intermembranous space ( 3 ). (diabetesjournals.org)
- Granzyme B can also cleave Bid to induce cytochrome c release and the intrinsic apoptotic pathway. (biolegend.com)
Mitochondria8
- In addition, we carried out immunohistochemical analysis to confirm Bax translocation into the mitochondria and activated p53 at Ser 392 . (springer.com)
- The intracellular calcium produces an avalanche of reactive oxygen species (ROS), leading to mitochondria-mediated apoptotic process, in particular, during such a pathological condition [ 5 , 6 , 7 ]. (mdpi.com)
- Smac release from mitochondria was induced in both cell types, but release of apoptosis-inducing factor and endonuclease G was detected only in TK6 cells. (aacrjournals.org)
- Other pro-apoptotic factors such as Smac (second mitochondria-derived activator of caspase)/DIABLO (direct inhibitor of apoptosis protein-binding protein with low pI), apoptosis-inducing factor and endonuclease G are also released from the mitochondria 8 . (ersjournals.com)
- First, the BH3-only Bax-interacting protein Bid, which is a substrate of caspase-8, becomes activated in the death receptor-mediated pathway and induces the release of cytochrome c from mitochondria. (bloodjournal.org)
- The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). (rupress.org)
- The identification of cytochrome c as an apoptogenic factor released from mitochondria marked a pivotal breakthrough in uncovering the importance of this organelle in the intrinsic pathway of apoptosis ( 3 ). (aacrjournals.org)
- Cytochrome c released from mitochondria is coupled to the activation of caspase-9, a key initiator caspase (1). (cellsignal.com)
Cleaves4
- Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. (abcam.com)
- Activated caspase-9 in turn cleaves and activates caspase-3. (nih.gov)
- Activated caspase 9 primary signaling occurs through caspase 3, which it cleaves and activates. (novusbio.com)
- During the assay, activated caspase-3 cleaves this substrate between DEVD and AMC, generating highly fluorescent AMC that can be detected using a fluorescence reader with excitation at 380 nm and emission between 420 - 460 nm. (cellsignal.com)
Tumor11
- Apaf-1 is important for tumor suppression and drug resistance because it plays a central role in DNA damage -induced apoptosis . (bvsalud.org)
- 4. The method of claim 1, wherein said polarized scorpion venom solution prevents cancer and tumor growth. (freepatentsonline.com)
- RESEARCH DESIGN AND METHODS Human and rat islets and INS-1 cells were exposed to a combination of proinflammatory cytokines (interleukin-1β, interferon-γ, and/or tumor necrosis factor-α). (diabetesjournals.org)
- Proinflammatory cytokines, particularly interleukin (IL)-1β in combination with interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α, have been implicated in the elimination of β-cells in type 1 diabetes ( 1 ). (diabetesjournals.org)
- CAAs provide fuel, growth factors, and cytokines and transdifferentiate into other stromal cells to alter tumor growth, metastasis, and drug responses. (jci.org)
- 4 One involves the ligation of death receptors, such as CD95 and tumor necrosis factor-receptor (TNF-R1), which on binding of the adapter protein FADD, recruit procaspase-8 into the death-inducing signaling complex. (bloodjournal.org)
- The extrinsic pathway is mediated by a variety of death receptor ligands, including tumor necrosis factor (TNF) and Fas ligand (FaSL), that trigger apoptosis by binding to cell surface receptors. (cdc.gov)
- Semiquantitative reverse transcription-PCR depicted increased expression of tumor necrosis factor-α and Fas ligand and the related death domains tumor necrosis factor receptor 1-associated death domain and Fas-associated death domain. (aacrjournals.org)
- The two molecular programs are known as the extrinsic pathway operating downstream of death receptors, such as Fas and the tumor necrosis factor receptor family, and the intrinsic pathway, which is activated by a diverse array of stress signals. (aacrjournals.org)
- It was found that a dihydroxylated water-soluble sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414). (aacrjournals.org)
- The extrinsic pathway is regulated by signaling through receptors of the Tumor Necrosis Factor receptor (TNFR) superfamily. (biolegend.com)
Signals3
- It is also becoming clear that mitosis and apoptosis are toggled or linked in some way and that the balance achieved depends on signals received from appropriate growth or survival factors. (wikipedia.org)
- The extrinsic pathway of apoptosis is triggered by external signals that activate cell surface death receptors, including Fas. (thefreelibrary.com)
- Weak external signals may also activate the intrinsic pathway of apoptosis. (wikipedia.org)
Cysteine protease1
- This cysteine protease family consists of more than 10 related members characterized by almost absolute specificity for aspartic acid in the P1 position. (biovendor.com)
Metabolism2
- In fact, perturbations in cell metabolism, growth factor availability, and genotoxic agents, which result in the loss of mitochondrial function, can induce cell death even in the absence of caspase activation. (aspetjournals.org)
- Lipin 1 plays a role in lipid metabolism in various tissues and cell types including liver, muscle, adipose tissues, and neuronal cell lines (2-4). (cellsignal.com)
Extrinsic2
- The extrinsic or death receptor pathway involves the activation of death receptors present in the cell membrane, such as Fas and tumour necrosis factor (TNF) receptor 1. (ersjournals.com)
- Extrinsic pathway signaling can also cross-activate mitochondrial release of cytochrome c through caspase 8-mediated cleavage of Bid , a pro-apoptotic member of the Bcl-2 family. (biolegend.com)
Stimuli2
- Another pathway that is triggered by a number of apoptotic stimuli such as anticancer drugs or irradiation is essentially controlled at the mitochondrion. (bloodjournal.org)
- How the apoptotic pathway is restricted in mature neurons and how these restrictions are overcome after pathological stimuli is unclear. (rupress.org)
Kinase14
- A critical regulator of autophagy induction is the kinase mTOR, which when activated, suppresses autophagy and when not activated promotes it. (wikipedia.org)
- Three related serine/threonine kinases, UNC-51-like kinase -1, -2, and -3 (ULK1, ULK2, UKL3), which play a similar role as the yeast Atg1, act downstream of the mTOR complex. (wikipedia.org)
- Here we used CRISPR-Cas9 mutagenesis to show that phagocyte intoxication involves uptake of dAdo via the human equilibrative nucleoside transporter 1, dAdo conversion to dAMP by deoxycytidine kinase and adenosine kinase, and signaling via subsequent dATP formation to activate caspase-3-induced cell death. (pnas.org)
- b) For GI/S cell cycle arrest, the p53-mediated pathway through p21 is involved, as well as the pRb gene-mediated pathway, c) Alteration of cyclin G1 and Wee-1 kinase genes may be related to the G2/M arrest induced by benzene exposure, d) DNA repair genes such as Rad50 and Rad51 are markedly downregulated in p53-KO mice. (thefreelibrary.com)
- The receptor for activated protein kinase C promotes cell growth, invasion and migration in cervical cancer. (amedeo.com)
- . 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)
- JNK and p38 alpha activate transcription of c-Jun , which, in turn, excites transcription of cyclin-dependent kinase 1 ( CDK1 ). (bio-rad.com)
- In addition, c-Alb activates protein kinase C, delta ( PKC delta ). (bio-rad.com)
- We observed that Aβ rapidly activates c-Jun N-terminal kinase (JNK). (jneurosci.org)
- Both PCI-2000 and PCI-2010, a tetrahydroxy bis-carbamate derivative of PCI-2000, result in increased levels of phosphorylated p38 mitogen-activated protein kinase. (aacrjournals.org)
- Inhibition of p38 mitogen-activated protein kinase phosphorylation resulted in a synergistic increase of PCI-2000 cytotoxicity. (aacrjournals.org)
- Treatment with this sapphyrin or PCI-2010, a congeneric tetrahydroxy bis-carbamate derivative, resulted in enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK), a stress-responsive protein kinase that participates in the regulation of apoptosis. (aacrjournals.org)
- Protease-activated receptor 1 (PAR-1)-induced GRO/CINC-1 release was mainly mediated by c-Jun N-terminal kinase (JNK) activation. (elsevier.com)
- Extracellular signal-regulated kinase 1/2 might be partially involved, but not p38 mitogen-activated protein kinase. (elsevier.com)
Effector5
- In the second tier, plant intracellular immune receptors of the nucleotide-binding leucine-rich repeat (NB-LRR) protein family can be activated either by direct binding of effectors or, alternatively, by effector action on an associated target protein that generates a "modified-self" molecule ( 1 , 2 ). (pnas.org)
- Effector-mediated NB-LRR activation results in effector-triggered immunity (ETI), a rapid and high-amplitude output significantly overlapping with MTI ( 1 ). (pnas.org)
- Through proteolytic cleavage, caspase-9 activates the effector caspase, caspase-3, leading to cleavage of numerous cellular targets and resulting in the systematic dismantling of the cell ( 4 ). (diabetesjournals.org)
- We confirmed that miR-125a-5p and miR-16-5p (both enriched in ADEV-IL-1β and ADEV-TNFα) targeted NTKR3 and its downstream effector Bcl2. (nature.com)
- 2004). These factors ultimately activate the effector protease, caspase-3, driving programmed cell death (Dragovich et al. (thefreelibrary.com)
Activation26
- Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. (uniprot.org)
- Animal NLRs are activated by MAMPs and by modified-self molecules in the form of danger-associated molecular patterns ( 6 ) and regulate inflammasome activation, autophagy, and cell death ( 7 ). (pnas.org)
- We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. (nih.gov)
- Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. (nih.gov)
- Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (nih.gov)
- Caspase-9, formerly called Apaf-3, binds to Apaf-1 in the presence of cytochrome c and dATP, which leads to caspase-9 activation. (biovendor.com)
- This, together with the observation that DRONC and DRICE were activated in distinct spatial and temporal patterns (see Figure 3A-3D), suggests that DRICE activation occurs through an unknown HID-, ARK-, DRONC-, dFADD-, and DREDD-independent mechanism. (nih.gov)
- The resulting Apaf-1/cytochrome c complex associates with the zymogen form of caspase-9 (Apaf-3) in the presence of dATP or ATP, promoting the autocatalytic activation of caspase-9. (creative-biogene.com)
- Animal PCD is primarily achieved by the activation of the Asp-specific Cys protease (caspase) cascade ( Bratton and Cohen, 2001 ). (plantphysiol.org)
- This promotes the activation of procaspase-9, which then activates procaspase-3, the most prevalent caspase in animal cells. (plantphysiol.org)
- Apoptosis was studied in roundworms and in the final stages of its cell death, there discovery of the death-inducing protease CED-3 activation became the cause of the apoptosis. (wikibooks.org)
- Activation of Bad was determined by Ser136 dephosphorylation, mitochondrial stress by changes in mitochondrial metabolic activity and cytochrome c release, downstream apoptotic signaling by activation of caspase-9 and -3, and DNA fragmentation. (diabetesjournals.org)
- Once in the cytosol, cytochrome c complexes with apoptosis-protease activating factor-1, which, in the presence of ATP, leads to activation of the initiator caspase, caspase-9. (diabetesjournals.org)
- Upon activation, caspase 9 activates caspase 3, whose action leads to the execution of apoptosis. (biomedcentral.com)
- Connection of the death ligand to its death receptor leads to activation of an adaptor protein called activated death domain and the subsequent activation of procaspase-8 or -10. (ersjournals.com)
- TNFα and IL-1β are key mediators of glial activation and neuronal damage, but the effects of these cytokines on the release or molecular composition of ADEVs is unknown. (nature.com)
- Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. (bloodjournal.org)
- 5 6 Once released, cytochrome c together with deoxyadenosine triphosphate binds to apoptotic protease-activating factor-1 (Apaf-1), leading to an unmasking of its caspase recruitment domain and the subsequent binding and autoproteolytic activation of procaspase-9. (bloodjournal.org)
- Multiple cellular stressors cause activation of the caspase proteases and apoptosis in neurons ( Putcha and Johnson, 2004 ). (rupress.org)
- Once in the cytosol, cytochrome c interacts with its adaptor molecule, Apaf-1, resulting in the recruitment, processing and activation of pro-caspase-9. (rsc.org)
- These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function. (rupress.org)
- Structural and Biochemical Basis of Apoptotic Activation by Smac/DIABLO. (tsinghua.edu.cn)
- In mammals, the execution of this pathway is governed by two molecular programs which ultimately lead to the activation of select members of the caspase (cysteinyl aspartate-specific protease) family. (aacrjournals.org)
- Activation of caspase-3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments. (cellsignal.com)
- Further studies demonstrated that PAR-1 activation, as well as application of recombinant GRO/CINC-1, protected astrocytes from C 2 -ceramide-induced cell death. (elsevier.com)
- The cell diversity is originated by cell differentiation, which has been attributed to the activation of specific transcription factors. (wikipedia.org)
Cleavage4
- In addition, 20 µM luteolin had a significant inhibitory effect on multi-heavy metal mixture-induced cleavage of caspase-9, caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein. (spandidos-publications.com)
- Apoptotic cells undergo various morphological changes, including cell shrinkage, membrane blebbing, cleavage of chromosomal DNA and the release of the membrane-bound apoptotic bodies. (ersjournals.com)
- 9 10 Second, caspase-9 can activate procaspase-8 via the caspase-3 and caspase-6 cascade, thus amplifying the receptor-derived signal and via Bid cleavage also the mitochondrial pathway. (bloodjournal.org)
- These proteases are synthesized as inactive proenzymes which, upon proteolytic cleavage at aspartate residues, form an active complex composed of two heterodimeric subunits. (rupress.org)
Cytosol1
- Cyt c in the cytosol catalyzes the oligomerization of apoptotic protease activating factor-1. (plantphysiol.org)
Neurons13
- Activated p53 and Bax mitochondrial translocation were detected in injured spinal neurons. (springer.com)
- By E2F and p53/TP53 in apoptotic neurons. (mybiosource.com)
- We show that as neurons mature, cytochrome c - mediated apoptosis progresses from inhibitor of apoptosis protein-dependent to -independent regulation because of a complete loss of Apaf-1 expression. (rupress.org)
- However, after DNA damage, mature neurons resynthesize Apaf-1 through the cell cycle-related E2F1 pathway and restore their apoptotic potential. (rupress.org)
- Surprisingly, we find that E2F1 is sufficient to induce Apaf-1 expression in developing but not mature neurons. (rupress.org)
- Rather, Apaf-1 up-regulation in mature neurons requires both chromatin derepression and E2F1 transcriptional activity. (rupress.org)
- This differential capacity of E2F1 to induce Apaf-1 transcription is because of the association of the Apaf-1 promoter with active chromatin in developing neurons and repressed chromatin in mature neurons. (rupress.org)
- These data specifically illustrate how the apoptotic pathway in mature neurons becomes increasingly restricted by a novel mechanism involving the regulation of chromatin structure. (rupress.org)
- Importantly, we identify chromatin modification as important mechanisms by which apoptotic resistance is regulated in maturing neurons. (rupress.org)
- Surprisingly, XIAP-deficient mature P28 neurons remained completely resistant to injection of cytochrome c ( Fig. 1 a ). (rupress.org)
- These results indicate that the apoptotic pathway in mature P28 neurons becomes further restricted by mechanisms independent of IAPs. (rupress.org)
- The survival of neurons is maintained primarily by neurotrophic factors that suppress the apoptotic program. (jneurosci.org)
- Here, we show that DP5/Harakiri, a Bcl-2 homology domain 3-only member of the Bcl-2 family, is induced in motoneurons after transection of the hypoglossal nerve in mice and in sympathetic neurons after nerve growth factor (NGF) withdrawal. (jneurosci.org)
Cytochrome c release2
- The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. (bloodjournal.org)
- 7 8 Activated Bid triggers a conformational change of another proapoptotic molecule, Bax, which leads to its oligomerization and subsequent insertion into the outer mitochondrial membrane and finally to cytochrome c release. (bloodjournal.org)
Cascade4
- Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. (nih.gov)
- Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. (nih.gov)
- caspase-9 thus is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (biovendor.com)
- An etoposide -treated DU145 prostate cancer cell exploding into a cascade of apoptotic bodies. (wikipedia.org)
Serine2
- AIF and the serine protease Omi catalyze caspase-independent downstream events in the apoptotic process. (rsc.org)
- Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type proteinase inhibitor that acts against a wide range of serine proteases through their nonproductive interaction with a P 1 residue in its first Kunitz-type domain ( 4 ). (aacrjournals.org)
Oligomerization2
Cellular5
- As such, control or modulation of apoptotic processes is favorable to picornaviruses, and this minireview will specifically focus on the modifications of cellular processes by picornaviruses that lead to downregulation of apoptosis. (asm.org)
- Cellular conditions experienced during energy-limited states - elevated calcium, shifts in cellular adenylate status, compromised mitochondrial membrane potential - are precisely those that trigger, at least in mammals, the mitochondrion to initiate opening of the permeability transition pore, to assemble additional protein release channels, and to release pro-apoptotic factors. (biologists.org)
- Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. (novusbio.com)
- Apoptotic cells do not release their cellular contents and are quickly engulfed by phagocytic cells, and therefore avoid triggering unnecessary inflammatory responses. (biolegend.com)
- The intrinsic pathway is triggered by detection of cellular stresses, such as DNA damage and hypoxia, or by the absence of signaling from growth factors, hormones, and cytokines. (biolegend.com)
Cell death17
- Owing to the fact that apoptosis causes minimal inflammation and damage to the tissue, apoptotic cell death-based therapy has been the centre of attraction for the development of anticancer drugs. (nature.com)
- 1 Cell death plays critical roles in regulating embryonic development, maintaining tissue homoeostasis, controlling immune function, tumour suppression and infection resistance. (nature.com)
- DNA damage-induced, p53-activated neuronal cell death has already been identified in several neurodegenerative diseases. (springer.com)
- In fact, the availability of growth factors is thought to define the size of various tissues by dictating the delicate balance between proliferation and cell death within a particular organ ( Conlon and Raff, 1999 ). (aspetjournals.org)
- Therefore, cell death can be categorized based on the method of initiation: 1) that which is initiated from cell surface death receptor engagement or 2) death arising from mitochondrial dysfunction. (aspetjournals.org)
- As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. (spandidos-publications.com)
- Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death. (spandidos-publications.com)
- It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is blocked by endogenous or exogenous factors such as viruses or mutations. (wikipedia.org)
- Some animals like embryos of the brine shrimp, Artemia franciscana , exhibit profound metabolic depression and survive anoxia at room temperature for years ( Clegg, 1997 ) with no evidence of apoptotic or necrotic cell death. (biologists.org)
- The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced β-cell death is unclear. (diabetesjournals.org)
- CONCLUSIONS Our findings demonstrate that the intrinsic mitochondrial apoptotic pathway contributes significantly to cytokine-induced β-cell death and suggest a functional role of calcineurin-mediated Bad Ser136 dephosphorylation and Bax activity in cytokine-induced apoptosis. (diabetesjournals.org)
- Apoptosis is an energy-dependent process in which dying cells activate a genetically encoded cell-death program. (diabetesjournals.org)
- Mammary gland development goes through different stages that depend on proper regulation of proliferation and programmed cell death (apoptosis) ( Fig. 1 A). Sex hormone-dependent cyclic organization of growth and survival provides the plasticity of the mammary gland that is needed for its function. (biologists.org)
- 1 Apoptosis, also known as programmed cell death, is the form of cell elimination commonly occurring during development as well as in many physiologic and pathologic processes. (bloodjournal.org)
- Neuronal cell death appears to occur through competition for trophic factors derived from target tissues, which may serve to select the proper set of neuronal connections ( Oppenheim, 1991 ). (jneurosci.org)
- 1. Programmed cell death is as needed for proper development as mitosis is. (biology-pages.info)
- The nature of cell death was apoptotic, as determined by annexin and DNA nick labeling. (aacrjournals.org)
Gene10
- Here, for the first time we present spontaneous mutations and recombinations of the Apaf-1 gene and its neighbouring sequences. (ac.ir)
- Inactivation of the Apaf-1 gene is implicated in disease progression and chemoresistance of some malignancies . (bvsalud.org)
- Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ultraviolet irradiation resistance-associated gene (UVRAG), is required for the induction of autophagy. (wikipedia.org)
- Still, neither the single-gene approach nor gene expression profiling alone has been shown to accurately reflect the complex network of responses that characterizes an apoptotic program. (aacrjournals.org)
- This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (creative-biogene.com)
- Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) - Caspase-7 (CASP7) is a human protein encoded by the CASP7 gene. (researchandmarkets.com)
- Here we report the isolation and characterization of TMS1 ( t arget of m ethylation-induced s ilencing), a novel CpG island-associated gene that becomes hypermethylated and silenced in cells overexpressing DNA cytosine-5-methyltransferase-1. (aacrjournals.org)
- On the basis of the results of large-scale gene expression studies, we conclude the following: a) Benzene induces DNA damage in cells at any phase of the cell cycle through myeloperoxidase and in the redox cycle, resulting in p53 expression through Raf-1 and cyclin D-interacting myb-like protein 1. (thefreelibrary.com)
- The abnormal development of adipose tissues caused by mutations in the lipin 1 gene results in lipodystrophy, a condition associated with low body fat, fatty liver, hypertriglyceridemia, and insulin resistance (1). (cellsignal.com)
- Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
Regulation2
- It has been shown that the expression of Mcl-1 in CLL is significantly associated with a failure to achieve complete remission following cytotoxic therapy, so regulation of Mcl-1 expression by coumarins could be one of the mechanisms of CLL chemotherapy. (intechopen.com)
- In this chapter, the cytotoxic activity of coumarins and their role in Mcl-1 regulation are discussed. (intechopen.com)
Receptor4
- Autocrine expression of the epidermal growth factor receptor ligand heparin-binding EGF-like growth factor in cervical cancer. (amedeo.com)
- Retinoids are thus ideal candidates for medical therapies, as the uptake of RA (and its closely related synthetic analogues) does not require a cell surface receptor [ 1 ]. (omicsonline.org)
- We report that thrombin and thrombin receptor agonist peptide (TRag) up-regulated secretion of the chemokine growth-regulated oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) in primary rat astrocytes in a concentration-dependent manner. (elsevier.com)
- These results demonstrate for the first time that PAR-1 plays an important role in anti-apoptosis in the brain by regulating the release of chemokine GRO/CINC-1, which gives a feedback through its receptor CXCR2 to preserve astrocytes from toxic insults. (elsevier.com)
Molecules4
- Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) pipeline Target constitutes close to 5 molecules. (researchandmarkets.com)
- Similarly, the universities portfolio in Preclinical and Discovery stages comprises 1 and 1 molecules, respectively. (researchandmarkets.com)
- TMS1 is localized to chromosome 16p11.2-12.1 and encodes a 22-kDa predicted protein containing a COOH-terminal caspase recruitment domain, a recently described protein interaction motif found in apoptotic signaling molecules. (aacrjournals.org)
- Overexpression of Bcl-2 1 and Fas-inhibitory molecules such as TOSO is the principle mechanism of apoptosis resistance in CLL cells. (intechopen.com)
Receptors4
- During the development process for Alzheimer's disease (AD), excessive activated extracellular glutamate receptors prompt changes in ion channels and signaling systems [ 5 , 6 , 7 ]. (mdpi.com)
- In the first tier, extracellular pattern recognition receptors (PRRs) bind conserved microbial-associated molecular pattern (MAMP) ligands, activating a complex host response that results in MAMP-triggered immunity (MTI). (pnas.org)
- The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions [ PMID: 11828422 , PMID: 12655292 ]. (ebi.ac.uk)
- Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. (rupress.org)
Inhibitor6
- an inhibitor of IAPs) was unable to induce apoptosis ( Fig. 1 a ). (rupress.org)
- Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells. (aacrjournals.org)
- It supports the neuroprotective action of activated protein C ( 10 ) and circulates in plasma as both free and in complex with C4b-binding protein (C4BP), which is an inhibitor of the classic complement pathway ( 11 ). (diabetesjournals.org)
- Importantly, a specific JNK inhibitor significantly abolished the protective action of PAR-1. (elsevier.com)
- It remains inactive in growing cells while it is associated with its inhibitor (ICAD, DNA fragmentation factor 45 kDa subunit, DFFA or DFF45) resulting into a complex ICAD-CAD. (wikipedia.org)
- Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
Transcription3
- Whereas histone acetyltransferase catalyzes the acetylation of histones and relaxes chromatin to increase the accessibility of transcription factors to the promoters of the target genes, HDACs remove the acetyl groups from histones and repress transcription [ 4 ]. (hindawi.com)
- Myogenic regulatory factors are muscle-specific helix-loop-helix transcription factors that regulate muscle-specific genes ( 12 , 25 ). (physiology.org)
- Activated p53 regulates transcription of apoptosis regulator Bax [ 16 ], apoptotic protease activating factor ( Apaf-1 ) [ 17 ] and Bcl-2 . (bio-rad.com)
Antibody2
- HeLa cell lysates (Human cervical epitheloid carcinoma, ATCC CCL-2.2) were probed with the polyclonal rabbit anti- APAF-1 antibody at a concentration of 0.5 µg/ml (lane 1), 0.25 µg/ml (lane 2) or in the presence of blocking peptide (lane 3). (antibodies-online.com)
- The Caspase 9 antibody was used by Krajewski's group to characterize caspase 9 mitochondrial release during cytochrome c-dependent apoptosis and ischemia in their neuronal cell culture models 1 . (novusbio.com)
Mitochondrial membrane4
- A JC-1 staining assay indicated that 20 µM luteolin inhibited the mitochondrial membrane potential-reducing effect of the multi-heavy metal mixture. (spandidos-publications.com)
- Therefore, permeabilization of the outer mitochondrial membrane (OMM) is considered a crucial event during the early phase of the apoptotic process. (rsc.org)
- The reducing equivalents produced through the TCA cycle fuel the electron transport chain component of the mitochondrial oxidative phosphorylation system (OXPHOS), wherein flow of electrons through respiratory complexes is linked to generation of a proton gradient across the inner mitochondrial membrane (IM) that is required for ATP production by F 1 F 0 ATP synthase. (frontiersin.org)
- This results in the increased permeability of the mitochondrial membrane, which is regulated by pro- and anti-apoptotic members of the Bcl-2 family (e.g. (biolegend.com)
Family5
- Apoptosis is mediated by caspase family proteases. (nih.gov)
- Anti-apoptotic Bcl-2 family members act to prevent cyt c release, whereas pro-apoptotic Bcl-2 family members promote such release ( Adams and Corey, 2001 ). (plantphysiol.org)
- Essential in this process is the caspase family of cysteine proteases ( 2 ). (diabetesjournals.org)
- In this study, we sought to identify which members of the Bcl-2 family contribute to Aβ-induced neuron death and to identify both the upstream and downstream components of this apoptotic pathway. (jneurosci.org)
- Broader overview of the BCL-2 family can be found in reviews published elsewhere ( 1 , 2 ). (aacrjournals.org)
Downregulation1
- The present results suggested luteolin exerts its inhibitory effects of on multi-heavy metal mixture induced cell apoptosis through downregulation of the ROS-activated mitochondrial pathway. (spandidos-publications.com)
20181
- The report 'Proprotein Convertase SubtilisinKexin Type 9 - Pipeline Review, H1 2018' outlays comprehensive information on the Proprotein Convertase Subtilisin/Kexin Type 9 (Proprotein Convertase 9 or Neural Apoptosis Regulated Convertase 1 or Subtilisin/Kexin Like Protease PC9 or PCSK9 or EC 3.4.21. (researchandmarkets.com)
Intracellular1
- In addition to viral proteases, the transmembrane 2B protein alters intracellular ion signaling, which may also modulate apoptosis. (asm.org)
Genes2
- To determine DNA damage-induced, p53-mediated apoptosis in spinal cord injury, we performed RT-PCR microarray and analyzed 84 DNA damaging and apoptotic genes. (springer.com)
- Genes involved in DNA damage and apoptosis were upregulated whereas anti-apoptotic genes were downregulated in injured spinal cords. (springer.com)