Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.
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.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Alkaloids derived from TYRAMINE combined with 3,4-dihydroxybenzaldehyde via a norbelladine pathway, including GALANTAMINE, lycorine and crinine. They are found in the Amaryllidaceae (LILIACEAE) plant family.
The functions and properties of living organisms, including both the physical and chemical factors and processes, supporting life in single- or multi-cell organisms from their origin through the progression of life.
Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.
The functions and activities of living organisms that support life in single- or multi-cellular organisms from their origin through the progression of life.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).
An order of nematodes of the subclass ADENOPHOREA. Its organisms commonly have a cylindrical esophagus. The superfamilies of this order are DIOCTOPHYMATOIDEA; MERMITHOIDEA; and TRICHUROIDEA.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
A genus of CRUSTACEA of the order ANOSTRACA, found in briny pools and lakes and often cultured for fish food. It has 168 chromosomes and differs from most crustaceans in that its blood contains hemoglobin.
One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.
Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products.
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)
Animals and plants which have, as their normal mode of reproduction, both male and female sex organs in the same individual.
A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.
Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.
A class of nucleotide translocases found abundantly in mitochondria that function as integral components of the inner mitochondrial membrane. They facilitate the exchange of ADP and ATP between the cytosol and the mitochondria, thereby linking the subcellular compartments of ATP production to those of ATP utilization.
Insects of the family Formicidae, very common and widespread, probably the most successful of all the insect groups. All ants are social insects, and most colonies contain three castes, queens, males, and workers. Their habits are often very elaborate and a great many studies have been made of ant behavior. Ants produce a number of secretions that function in offense, defense, and communication. (From Borror, et al., An Introduction to the Study of Insects, 4th ed, p676)
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.

Small molecule inhibitors of Apaf-1-related caspase- 3/-9 activation that control mitochondrial-dependent apoptosis. (1/62)

Apoptosis is a biological process relevant to human disease states that is strongly regulated through protein-protein complex formation. These complexes represent interesting points of chemical intervention for the development of molecules that could modulate cellular apoptosis. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated Apaf-1 (apoptotic protease-activating factor), dATP and procaspase-9 that link mitochondria disfunction with activation of the effector caspases and in turn is of interest for the development of apoptotic modulators. In the present study we describe the identification of compounds that inhibit the apoptosome-mediated activation of procaspase-9 from the screening of a diversity-oriented chemical library. The active compounds rescued from the library were chemically optimised to obtain molecules that bind to both recombinant and human endogenous Apaf-1 in a cytochrome c-noncompetitive mechanism that inhibits the recruitment of procaspase-9 by the apoptosome. These newly identified Apaf-1 ligands decrease the apoptotic phenotype in mitochondrial-mediated models of cellular apoptosis.  (+info)

ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity. (2/62)

In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenotypic series of these alleles, we identified helical domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic activity. Interestingly, the WD40 region may also have an unanticipated positive requirement for the apoptotic activity of ARK. Considering structural information, we discuss the roles of these domains for assembly and activity of the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the absence of apoptotic signals, and pro-apoptotic in the presence of such signals. Furthermore, a defined null allele reveals that ark is required for most, but not all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.  (+info)

Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons. (3/62)

Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases in these neurons remains debated. We find that the ability of sympathetic neurons to undergo apoptosis in response to nerve growth factor (NGF) deprivation is completely dependent on having an intact apoptosome pathway. Genetic deletion of Apaf-1, caspase-9, or caspase-3 prevents apoptosis after NGF deprivation, and importantly, allows these neurons to recover and survive long-term following readdition of NGF. The inability of caspase-3 deficient sympathetic neurons to undergo apoptosis is particularly striking, as apoptosis in dermal fibroblasts and cortical neurons proceeds even in the absence of caspase-3. Our results show that in contrast to dermal fibroblasts and cortical neurons, sympathetic neurons express no detectable levels of caspase-7. The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic neurons with a markedly increased control over their apoptotic pathway.  (+info)

The marine product cephalostatin 1 activates an endoplasmic reticulum stress-specific and apoptosome-independent apoptotic signaling pathway. (4/62)

Cephalostatin 1, a bis-steroidal marine natural product, has been reported to induce apoptosis without the requirement of an active caspase-8 or mitochondrial cytochrome c release and apoptosome formation. Here we show that despite the absence of these events, caspase-9 activation is essential for cephalostatin 1-induced apoptosis. Cephalostatin 1 initiates a rapid endoplasmic reticulum stress response characterized by phosphorylation of eukaryotic initiation factor-2 alpha-subunit and increased expression of the chaperone immunoglobulin heavy chain-binding protein GRP78 as well as the transcription factor C/EBP homologous protein (CHOP)/GADD153. Cephalostatin 1 activates apoptosis signal-regulating kinase 1 and c-Jun N-terminal kinase (JNK). However, this pathway does not play a major role in cephalostatin 1-induced apoptosis, as assessed by stable expression of a dominant negative apoptosis signal-regulating kinase 1. Importantly, the endoplasmic reticulum-associated caspase-4 is required and as shown by biochemical and genetic inhibition experiments, acts upstream of caspase-9 in cephalostatin-induced apoptosis.  (+info)

Apoptosome: a platform for the activation of initiator caspases. (5/62)

Apoptosome refers to the adaptor protein complex that mediates the activation of an initiator caspase at the onset of apoptosis. In mammalian cells, caspase-9, caspase-8, and caspase-2 rely on the apoptotic protease-activating factor 1 (Apaf-1)-apoptosome, death-inducing signaling complex (DISC), and PIDDosome, respectively, for activation. In Drosophila, activation of the caspase-9 homolog Dronc requires assembly of an apoptosome comprised of Dark/Hac-1/Dapaf-1. In Caenorhabditis elegans, activation of the caspase CED-3 is facilitated by the CED-4-apoptosome. Recent biochemical and structural investigation revealed significant insights into the assembly and function of the various apoptosomes. Nonetheless, conclusive mechanisms by which the initiator caspases are activated by the apoptosomes remain elusive. Several models have been proposed to explain the activation process. The induced proximity model summarizes the general process of initiator caspase activation. The proximity-driven dimerization model describes how initiator caspases respond to induced proximity and offers an explanation for their activation. Regardless of how initiator caspases are activated, enhanced activity must be correlated with altered active site conformation. The induced conformation model posits that the activated conformation for the active site of a given initiator caspase is attained through direct interaction with the apoptosome or through homo-oligomerization facilitated by the apoptosome.  (+info)

Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. (6/62)

Glioblastoma (GBM) is an astrocytic brain tumor characterized by an aggressive clinical course and intense resistance to all therapeutic modalities. Here, we report the identification and functional characterization of Bcl2L12 (Bcl2-like-12) that is robustly expressed in nearly all human primary GBMs examined. Enforced Bcl2L12 expression confers marked apoptosis resistance in primary cortical astrocytes, and, conversely, its RNA interference (RNAi)-mediated knockdown sensitizes human glioma cell lines toward apoptosis in vitro and impairs tumor growth with increased intratumoral apoptosis in vivo. Mechanistically, Bcl2L12 expression does not affect cytochrome c release or apoptosome-driven caspase-9 activation, but instead inhibits post-mitochondrial apoptosis signaling at the level of effector caspase activation. One of Bcl2L12's mechanisms of action stems from its ability to interact with and neutralize caspase-7. Notably, while enforced Bcl2L12 expression inhibits apoptosis, it also engenders a pronecrotic state, which mirrors the cellular phenotype elicited by genetic or pharmacologic inhibition of post-mitochondrial apoptosis molecules. Thus, Bcl2L12 contributes to the classical tumor biological features of GBM such as intense apoptosis resistance and florid necrosis, and may provide a target for enhanced therapeutic responsiveness of this lethal cancer.  (+info)

Essential postmitochondrial function of p53 uncovered in DNA damage-induced apoptosis in neurons. (7/62)

In postmitotic sympathetic neurons, unlike most mitotic cells, death by apoptosis requires not only the release of cytochrome c from the mitochondria, but also an additional step to relieve X-linked inhibitor of apoptosis protein (XIAP)'s inhibition of caspases. Here, we examined the mechanism by which XIAP is inactivated following DNA damage and found that it is achieved by a mechanism completely different from that following apoptosis by nerve growth factor (NGF) deprivation. NGF deprivation relieves XIAP by selectively degrading it, whereas DNA damage overcomes XIAP via a p53-mediated induction of Apaf-1. Unlike wild-type neurons, p53-deficient neurons fail to overcome XIAP and remain resistant to cytochrome c after DNA damage. Restoring Apaf-1 induction in p53-deficient neurons is sufficient to overcome XIAP and sensitize cells to cytochrome c. Although a role for p53 in apoptosis upstream of cytochrome c release has been well established, this study uncovers an additional, essential role for p53 in regulating caspase activation downstream of mitochondria following DNA damage in neurons.  (+info)

Analysis of apoptosome dysregulation in pancreatic cancer and of its role in chemoresistance. (8/62)

The apoptosome is a multiprotein complex mediating the mitochondrial pathway of cell death. Its importance during development has been clearly demonstrated by knocking out key genes in mouse. APAF1 is the core protein of the apoptosome and its dosage is also critical in various cancer types, i.e., melanoma, germ line tumor, gastrointestinal cancer and B-type chronic lymphocytic leukemia. This is generally due to inactivation of the APAF1 locus by epigenetic phenomena or by activity of promoter regulators. We investigated the putative roles of the apoptosome in pancreatic ductal adenocarcinoma (PDAC). We found that both APAF1 mRNA and protein are dysregulated in human PDAC samples. Similarly, several PDAC cell lines exhibited variable levels of both APAF1 protein and mRNA. The response to cell death induction and its biochemical features were assessed by treatment of each line with commonly used chemotherapeutic agents. We found that the apoptosome pathway was not functional in most cell lines upon cytochrome c release from mitochondria. In addition, we restored APAF1 and Caspase-9 dosage in Panc-1 cells, where the apoptosome is downregulated, by overexpressing the murine cDNA of the two molecules, and we improved the death response to chemotherapeutic agents.  (+info)

TY - JOUR. T1 - Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. AU - Mazroui, Rachid. AU - Di Marco, Sergio. AU - Clair, Eveline. AU - Von Roretz, Christopher. AU - Tenenbaum, Scott A.. AU - Keene, Jack D.. AU - Saleh, Maya. AU - Gallouzi, Imed Eddine. PY - 2008/1/14. Y1 - 2008/1/14. N2 - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is ...
Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a molecular timer that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may ...
Apoptotic signaling is altered at many loci in cancer cells. Although many tumors develop resistance to cytochrome c-induced apoptosis, we have discovered that breast cancer cells exhibit a unique hypersensitivity to cytochrome c-induced apoptosis. Interestingly, this sensitivity is not due to changes in core apoptosomal proteins ( 44) but is due to a PHAPI-mediated posttranslational event that enhances the recruitment of caspase-9 to the Apaf-1 CARD. These findings have the potential to affect breast cancer chemotherapy through the development of apoptosome activators or cytochrome c mimetics as shown, in principle, by the fact that malignant mammary epithelial cells could be more easily killed by cytosolic cytochrome c than their normal counterparts.. PHAPI-mediated increase in caspase activation in breast cancer. Whereas many inhibitory signaling pathways converge on the apoptosome, there are very few physiologic/pathologic examples of enhanced apoptosome activation. Our data suggest that ...
TY - JOUR. T1 - Negative regulation of the Apaf-1 apoptosome by Hsp70. AU - Saleh, Ayman. AU - Srinivasula, Srinivasa M.. AU - Balkir, Levent. AU - Robbins, Paul D.. AU - Alnemri, Emad S.. N1 - Funding Information: ACKNOWLEDGEMENTS We thank the members of Robbins laboratory, especially M. Serrano, B. Baldwin, T. Kenniston and J. Mai, for technical support. We also thank Y. Lazebnik and S. H. Kaufmann for Apaf-1 and caspase-9 antibodies, respectively, and R. Morimoto for hsp70 cDNA. This work was supported by NIH grants AG14357 and AG13487 (to E.S.A.) and CA55227 (to P.D.R.). Correspondence and requests for materials should be addressed to E.S.A.. PY - 2000/8. Y1 - 2000/8. N2 - Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the caspase-recruitment ...
Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the ca …
Common Atom functions. module Language.Atom.Common ( -- * Timers Timer , timer , startTimer , startTimerIf , timerDone -- * One Shots , oneShotRise , oneShotFall -- * Debouncing , debounce -- * Lookup Tables , lookupTable -- * Hysteresis , hysteresis ) where import Data.Word import Language.Atom.Language -- , A Timer. data Timer = Timer (V Word64) -- , Creates a new timer. timer :: Name -, Atom Timer timer name = do timer ,- word64 name 0 return $ Timer timer -- , Starts a Timer. A timer can be restarted at any time. startTimer :: Timer -, E Word64 -, Atom () startTimer t = startTimerIf t true -- , Conditionally start a Timer. startTimerIf :: Timer -, E Bool -, E Word64 -, Atom () startTimerIf (Timer t) a time = t ,== mux a (clock + time) (value t) -- , True when a timer has completed. timerDone :: Timer -, E Bool timerDone (Timer t) = value t ,=. clock -- , One-shot on a rising transition. oneShotRise :: E Bool -, Atom (E Bool) oneShotRise a = do last ,- bool last False last ,== a return $ ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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What is MAC-ContentionResolutionTimer?,Which timer is started after msg3 is transmitted?,What if two UE attempted RA with the same RA preamble sequence on the same RA channel?,Type of contention Resolution process?,Why the macCRT timer is required?,How does ContentionResolutionTimer work in NB-IOT?,Which msg body in you can find macContentionResolutionTimer ?,What happened when macContentionResolutionTimer is expire?,What is the start and end activity of macContentionResolutionTimer?
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Bcl-xL is an antiapoptotic Bcl-2 family member that is required for embryonic development and can contribute to cancer cell survival (Letai, 2008; Hardwick and Youle, 2009). The traditional viewpoint is that anti- and proapoptotic Bcl-2 family proteins actively engage each other to determine cell fate after a death stimulus (Galonek and Hardwick, 2006; Youle and Strasser, 2008). The best-characterized cell survival activity of Bcl-xL is its ability to inhibit Bax-induced pores in the outer mitochondrial membrane (Billen et al., 2008). In this manner, Bcl-xL prevents release of mitochondrial cytochrome c into the cytoplasm, where cytochrome c induces apoptosome formation to trigger caspase-dependent death of mammalian cells. Attention has been focused on the functional interactions and the binding specificities between anti- and proapoptotic Bcl-2-related proteins, leading to new therapeutic strategies (Oltersdorf et al., 2005).. The evolutionary conservation of Bcl-2-like proteins cannot be ...
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I am not sure if this is even a valid bug; my brother killed another player in Stendhal 1.05 (private server) some time ago and he was waiting for the 2-week-expiration. He told me that apparently the timer has been reset to 2 weeks whenever he bought an outfit ( http://stendhalgame.org/wiki/Stendhal_Games#Hiring_special_outfits ) and that outfit expired. It might also have been a server restart which resetted the timer. Whatever it was: if he is right and didnt attack anyone, there seems to be a bug which resets the timer.. I know that bug reports like this one are not as helpful as others, but if this is a valid bug, the report might help anyway. ;-). ToBeFree ...
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The apoptosome is the cellular structure that facilitates programmed cell death. A new 3D map of it lays groundwork for future drug development.
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Create a Countdown Timer that counts down in seconds, minutes, hours and days to any date, with time zone support. It also counts up from a past date.
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Product prices and availability are accurate as of the date/time indicated and are subject to change. Any price and availability information displayed on [relevant Amazon Site(s), as applicable] at the time of purchase will apply to the purchase of this product. ...
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The apoptotic protease-activating factor 1 (Apaf-1) split luciferase biosensor continues to be used like a biological tool for the detection of early stage of apoptosis. and in human being diseases, the systems involved in this technique and the advancement of assays to recognize drug-like molecules that could be therapeutically useful possess drawn a whole lot of interest in the field. To day, many assays ideal for high-throughput testing have already been used and made for the detection of apoptosis. Each one uses particular feature of apoptosis pathway (whether intrinsic or extrinsic). Nevertheless, until the advancement of the Apaf-1 break up luciferase complementary assay, non-e could be utilized to monitor apoptosome development inside the cell loss of life signaling pathway [7,8,9]. With this novel split luciferase reporter, Nluc/Apaf-1 and Cluc/Apaf-1, the N-terminal and C-terminal fragments of luciferase, are genetically fused to the N-terminal site of Apaf-1 [10,11]. Here, we extended ...
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This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator ...
Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase-9 ... Zou H, Li Y, Liu X, Wang X (Apr 1999). "An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates ... Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". ... The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may ...
2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22: 269-275 Eckelman BP, Salvesen GS. (2006) The human anti- ... Biochem J 409, 461-469 Riedl, S. J. and Salvesen, G. S. (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol ...
Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". ...
2000). Negative regulation of the Apaf-1 apoptosome by Hsp70. Nature Cell Biol 2: 476-483. Fujita, K and Srinivasula SM. (2009 ... "Negative regulation of the Apaf-1 apoptosome by Hsp70". Nature Cell Biology. 2 (8): 476-483. doi:10.1038/35019510. ISSN 1465- ...
Histone H1.2 also forms a complex with the apoptosome, possibly regulating its formation. GRCh38: Ensembl release 89: ...
Hu Q, Wu D, Chen W, Yan Z, Shi Y (May 2013). "Proteolytic processing of the caspase-9 zymogen is required for apoptosome- ... Processing occurs when the apoptosome binds to pro-caspase-9 as apaf-1 assists in the autoproteolytic processing of the zymogen ... Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW (2002). "Three-dimensional structure of the apoptosome: implications ... Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which then cleaves ...
Cytochrome c promotes the activation of caspase-9 through the formation of the apoptosome. Once caspase-9 is activated, it can ...
Biology portal Apoptosis Apoptosome Bcl-2 Emricasan Metacaspase Paracaspase Pyroptosis The Proteolysis Map Programmed cell ... This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator ... during extrinsic apoptosis The apoptosome during intrinsic apoptosis The inflammasome during pyroptosis Once appropriately ...
Analogous to the apoptosome, which activates apoptotic cascades, the inflammasome activates a pyroptotic inflammatory cascade. ...
... forming a complex called apoptosome. The activation of caspase 3 and 9 by the apoptosome starts a proteolitic cascade that ...
"A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of ...
March 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". ... March 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". ...
... inhibits this process by blocking the recruitment of procaspase-9 to the Apaf-1/dATP/cytochrome c apoptosome complex. It ... "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome". Nature Cell ... which then recruits Apaf-1 and dATP/ATP into an apoptosome complex. This complex then cleaves procaspase-9, activating caspase- ...
"Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome". ...
This implies that DCC regulates a novel pathway for caspase activation, and that it is one that is apoptosome-independent. To ... This causes the activation of caspase-3 through caspase-9, and initiates apoptosis without the formation of an apoptosome or ...
... which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
These components are essential for forming a ternary complex called the apoptosome that activates Caspase-3 downstream of the ...
The Cytochrome C assembles an apoptosome which activates the Caspase-9 and initiates an executioner Caspase cascade, ...
... may be activated by proteolysis through its association with a protein complex that forms apoptosome, or by granzyme B, or via ...
... that cytochrome c remains within the inner mitochondrial membrane and hence does not trigger the production of an apoptosome in ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ...
Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ...
Apoptosis Apoptosome Bcl-2 homologous antagonist killer (BAK) Bcl-2-associated X protein (BAX) Bcl-xL BH3 interacting domain ...
... that precedes the release of the cytochrome c complex from the mitochondria and the formation of the apoptosome. The presence ... and Bcl-xL and up-regulates the pro-apoptotic proteins Bax and Bad that ultimately lead to the formation of the apoptosome. PD1 ...
Apoptosis Apoptosome Bcl-2 BH3 interacting domain death agonist (BID) Caspases Cytochrome c Noxa Mitochondrion p53 upregulated ...
... which is one of the parts needed to activate caspase-9 via the apoptosome), Smac/Diablo and Omi/HtrA2 (which suppress the ...
The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm ... The stable APAF-1 and cytochrome mutimeric complex fit this description, and is now called the apoptosome. The apoptosome was ... Recent structural studies of apoptosome prove that Apaf-1-ALT cannot form apoptosome as it misses key structural components for ... Because the resolution of the apoptosome structure was relatively low, two controversial models for apoptosome assembly were ...
"Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm ... The stable APAF-1 and cytochrome mutimeric complex fit this description, and is now called the apoptosome. The apoptosome was ... Recent structural studies of apoptosome prove that Apaf-1-ALT cannot form apoptosome as it misses key structural components for ... Because the resolution of the apoptosome structure was relatively low, two controversial models for apoptosome assembly were ...
... c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. ... Negative regulation of the Apaf-1 apoptosome by Hsp70 Nat Cell Biol. 2000 Aug;2(8):476-83. doi: 10.1038/35019510. ... of Apaf-1 and through inhibition of apoptosome formation. The interaction between Hsp70 and Apaf-1 prevents oligomerization of ... c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. ...
A near atomic structure of the active human apoptosome.. Cheng, T.C., Hong, C., Akey, I.V., Yuan, S., Akey, C.W.. (2016) Elife ... 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, ... In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near ... In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near ...
Researchers from Boston University School of Medicine have for the first time mapped an active human apoptosome. ... When active the apoptosome is a dynamic molecular machine with three to five protease molecules tethered to it at any given ... According to the researchers the apoptosome is a wheel-like structure with seven spokes. On top of the wheel is a spiral-shaped ... A soluble protease is in turn cleaved and activated by the active apoptosome and this soluble protease then targets cellular ...
... caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic ... A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement ... This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless ... Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of ...
Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons.. Wright ... Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases ... deprivation is completely dependent on having an intact apoptosome pathway. Genetic deletion of Apaf-1, caspase-9, or caspase-3 ... The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic ...
A cryo-electron microscopy model of the active human apoptosome illuminates how this wheel of death binds the protease ... 5) The authors structure of the platform of the pc-9 bound apoptosome and the unbound apoptosome recently reported by Zhou et ... The apoptosome and pc-9 activation. We have presented a structure for the central hub and extended arms of an active apoptosome ... Model of the active apoptosome.. (A, C) Top views are shown of the heptameric platform from the apoptosome model, with and ...
Autoprocessing of procaspase-9 reduces its affinity for the apoptosome. (A) Apoptosome complexes were assembled with decreasing ... E, F) Apoptosome-bound T7-tagged C9-p35/p12 or ProC9-TM were incubated with T7-tagged ProC9*-R56A and either T7-tagged ProC3* ... Each bar represents the mean of four separate experiments±s.e.m. (B) KM values for apoptosome-bound C9-p35/p12 (25 nM) and ... B) The initial velocities (V0) of apoptosome-bound C9-p35/p12, ProC9-TM, and C9-p35/p12-R56A on the substrate ProC3 were ...
This dysfunctional apoptosome activity was not correlated with any decrease of apoptosome component factors, but it was linked ... Here, we show that the apoptosome deficiency was observed in chemoresistant NSCLC NCI-H460 cells. No deficient apoptosome ... on the apoptosome activity of H460 cells and saw the low apoptosome activity dramatically reversed (Fig. 2C) ⇓ . Surprisingly, ... This apoptosome recruits and activates caspase-9, which in turn activates the executioner caspases, caspase-3 and caspase-7 (7 ...
Cytochrome c-mediated activation of the apoptosome was very efficient in naïve cell extracts as the apoptosome-processed, p35- ... Apoptosome-mediated cleavage of caspase-9 generates a 35-kD and a 12-kD fragment (Liu et al., 1996; Cain et al., 2002). ... Efficiency of apoptosome sets the threshold for IAPs to inhibit apoptosis in cells. If the differential ability of endogenous ... To reduce apoptosome function in naïve cells, we simply decreased the amount of exogenous cytochrome c, thereby limiting the ...
hccs downregulation induces apoptosome-independent caspase-9 activation in mitochondriaA-C. TUNEL assays on st30 embryos co- ... Mentions: Non-canonical apoptosome-independent caspase-9 activation has been observed in few specific conditions (Hao et al, ... Mentions: Non-canonical apoptosome-independent caspase-9 activation has been observed in few specific conditions (Hao et al, ... fig05: hccs downregulation induces apoptosome-independent caspase-9 activation in mitochondriaA-C. TUNEL assays on st30 embryos ...
Formation of apoptosome (Homo sapiens) * Regulation of the apoptosome activity (Homo sapiens) * UACA binds apoptosome (Homo ... Mouse Uaca, showing both cytoplasmic and perinuclear/nuclear localization, was suggested to translocate Apaf1-apoptosome to the ... thereby acting as a stabilizer for the apoptosome (Sakai T et al. 2004). Uaca was shown to induce apoptosis in mammalian cells ...
"Apoptosomes" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9. ... This graph shows the total number of publications written about "Apoptosomes" by people in this website by year, and whether " ... Below are the most recent publications written about "Apoptosomes" by people in Profiles. ...
apoptosome. id: GO:0043293. name: apoptosome. namespace: cellular_component. type: go. obsolete: False. ...
Apoptosome Formation - Duration: 2 minutes, 21 seconds.. *9,932 views. *5 years ago ...
... caspase-8 cleaves and activates caspase-9 in an apoptosome-independent manner. Interestingly, caspase-8-cleaved caspase-9 ... The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the ... induced lysosomal membrane permeabilization but failed to activate the effector caspases whereas apoptosome-dependent ... The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the ...
Diarylurea Compounds Inhibit Caspase Activation by Preventing the Formation of the Active 700-Kilodalton Apoptosome Complex ... Diarylurea Compounds Inhibit Caspase Activation by Preventing the Formation of the Active 700-Kilodalton Apoptosome Complex ...
Saleh, A, Srinivasula, SM, Balkir, L, Robbins, PD & Alnemri, ES 2000, Negative regulation of the Apaf-1 apoptosome by Hsp70, ... Negative regulation of the Apaf-1 apoptosome by Hsp70. Ayman Saleh, Srinivasa M. Srinivasula, Levent Balkir, Paul D. Robbins, ... Negative regulation of the Apaf-1 apoptosome by Hsp70. / Saleh, Ayman; Srinivasula, Srinivasa M.; Balkir, Levent; Robbins, Paul ... Dive into the research topics of Negative regulation of the Apaf-1 apoptosome by Hsp70. Together they form a unique ...
Work on the assembly and function of DARK, the apoptosome of D. melanogaster, has indicated that cyt-c is not required for its ... Cyt-c and apoptosome assembly. A classic downstream effect of the mitochondrial release of pro-apoptotic factors is the cyt-c ... Yu, X., Wang, L., Acehan, D., Wang, X. and Akey, C. W. (2006). Three-dimensional structure of a double apoptosome formed by the ... Chereau, D., Zou, H., Spada, A. P. and Wu, J. C. (2005). A nucleotide binding site in caspase-9 regulates apoptosome activation ...
... the apoptosome - that monitors cellular health. Extracellular regulatory mechanisms are discussed, as well as the intracellular ... Apoptosome. A large multimeric protein complex of apoptotic protease-activating factor 1 (APAF1) that recognizes cytochrome c ... Kim, H. E., Du, F., Fang, M. & Wang, X. Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and ... Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141, 446-457 (2010). ...
Proximity-induced caspase-9 activation on a DNA origami-based synthetic apoptosome. Bas J. H. M. Rosier, Albert J. Markvoort, ... for the systematic analysis of signalling proteins by engineering a synthetic DNA origami-based version of the apoptosome, a ...
Kuwano Y, Gallouzi I, Gorospe M. Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In Apoptosome: An Up ... Role of the RNA-binding protein HuR in apoptosis and apoptosome function. Apoptosome: An Up-and-coming Therapeutical Tool. ... Kuwano, Y., Gallouzi, I., & Gorospe, M. (2010). Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In ... Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands, 2010. p. 203-220.. Research output: Chapter in Book/ ...
Apoptosome Formation. Once cytochrome c is released into the cytoplasm, it binds WD40 repeats in the C-terminus of the adaptor ... Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J ... Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. Embo J. 2001; 20 ... Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol. ...
This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator ...
... approximately 700-kDa apoptosome complex and caspase activation. Using diarylureas to inhibit the formation of the apoptosome ... Thus, these compounds provide a novel specific tool to investigate the role of the apoptosome in mitochondrion-dependent death ... Once in the cytosol, cytochrome c triggers the formation of a caspase-activating protein complex called the apoptosome, whereas ... inhibits apoptosis by blocking the activation of the initiator caspase 9 by directly inhibiting the formation of the apoptosome ...
The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the ... The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the ... "Apoptosome-Independent Activation of the Lysosomal Cell Death Pathway by Caspase-9." Molecular and Cellular Biology, vol. 26, ... "Apoptosome-Independent Activation of the Lysosomal Cell Death Pathway by Caspase-9." Molecular and Cellular Biology 26 (21): ...
... apoptosome (a multiprotein caspase activating complex). Upon formation of the apoptosome complex, the key constituent of ... Shi Y . Mechanical aspects of apoptosome assembly. Curr Opin Cell Biol 2006; 18: 677-684. ... The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to ... apoptosome. This complex consists of caspase-9, Apaf-1 and cytochrome c which activates effector caspases and executes ...
... apoptosome, which seems to amplify rather than initiate the caspase cascade. ... Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. ... Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. ... apoptosome, which seems to amplify rather than initiate the caspase cascade. ...
The apoptosome. Extrinsic death pathway.. · Oncogenes and cancer. Classes of oncogenes. Mechanisms of proto-oncogenes ... The apoptosome. Extrinsic death pathway.. · Oncogenes and cancer. Classes of oncogenes. Mechanisms of proto-oncogenes ...
The binding of cytochrome c to Apaf-1 forms apoptosomes.. *Apoptosomes bind to caspase-9 and activates it. Caspase-9 is a ...
  • In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of an apoptosome. (wikipedia.org)
  • An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. (wikipedia.org)
  • The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic transmission electron microscopy in 2002, revealing a heptameric wheel-like particle with 7-fold symmetry. (wikipedia.org)
  • Recently, a medium resolution (9.5 Ångström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. (wikipedia.org)
  • The stable APAF-1 and cytochrome mutimeric complex fit this description, and is now called the apoptosome. (wikipedia.org)
  • The formation of the apoptosome requires the presence of ATP/dATP and cytochrome c in the cytosol. (wikipedia.org)
  • Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. (nih.gov)
  • These steps work in concert to trigger the assembly of the apoptosome: a large wheel-like complex that contains seven copies each of Apaf-1 and cytochrome c. (elifesciences.org)
  • We found that the cytochrome c /apoptotic protease-activating factor-1 (apoptosome)-dependent caspase activation is deficient in human non-small cell lung cancer (NSCLC) NCI-H460 cells. (aacrjournals.org)
  • The liberated cytochrome c , along with adenine nucleotides, initiates formation of an apoptosome consisting of Apaf-1 3 oligomers. (aacrjournals.org)
  • Cytochrome c , Apaf-1, and procaspase-9 oligomerize to form the apoptosome complex, resulting in the activation of caspase-9. (rupress.org)
  • The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the activation of caspase-9 during apoptosis. (ox.ac.uk)
  • Once in the cytosol, cytochrome c triggers the formation of a caspase-activating protein complex called the apoptosome, whereas Smac/Diablo and Omi/htra2 antagonize the caspase inhibitory effect of inhibitor of apoptosis proteins (IAPs). (ox.ac.uk)
  • Here, we identify diarylurea compounds as effective inhibitors of the cytochrome c-induced formation of the active, approximately 700-kDa apoptosome complex and caspase activation. (ox.ac.uk)
  • Using diarylureas to inhibit the formation of the apoptosome complex, we demonstrated that cytochrome c, rather than IAP antagonists, is the major mitochondrial caspase activation factor in tumor cells treated with tumor necrosis factor. (ox.ac.uk)
  • Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. (ox.ac.uk)
  • We conclude that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 'apoptosome', which seems to amplify rather than initiate the caspase cascade. (ox.ac.uk)
  • The binding of cytochrome c to Apaf-1 forms apoptosomes. (wikibooks.org)
  • Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. (aacrjournals.org)
  • Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c -induced apoptosome activation, further promoting chemotherapeutic resistance. (aacrjournals.org)
  • Cytochrome c binds with other molecules outside the mitochondria to form a protein called an apoptosome. (redorbit.com)
  • They found that neuroglobin binds to cytochrome c and prevents it from forming an apoptosome. (redorbit.com)
  • Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. (wikipedia.org)
  • Although this normal programmed cell death (PCD) can occur by distinct morphological pathways ( Clarke, 1990 , 1998 ), the biochemical and molecular pathways involved have been generally considered to require a relatively conserved core of so-called "proapoptotic" genes comprised of Bcl-2 family members, the apoptosome (cytochrome c , Apaf-1, caspase 9) and downstream caspases (e.g., caspase-3). (jneurosci.org)
  • The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. (aacrjournals.org)
  • The activation of effector caspases occurs downstream of the activation of initiator caspases (CED‐3, Dronc and caspase‐9), which occurs on the formation of the apoptosome, a protein complex contaning CED‐4, Ark/Dark and Apaf‐1, and cytochrome c . (els.net)
  • In Drosophila , the importance of cytochrome c and Bcl‐2 family members (Debcl/Buffy) for apoptosome formation and caspase activation is still not clear. (els.net)
  • Cytochrome c induces the heptamerization of the cytosolic protein Apaf‐1, which binds procaspase‐9 to form the active apoptosome complex for cleavage of effector caspases, whereas SMAC and HtrA2 act as inhibitors of IAPs. (els.net)
  • The complex of procaspase-9, cytochrome c, and Apaf-1 is known as the apoptosome. (bloodjournal.org)
  • A crucial step controlling the apoptosome pathway is the release of cytochrome c. (bloodjournal.org)
  • 2011 ). Upon release, cytochrome c and dATP bind to apoptotic proteinase-activating factor-1 (Apaf-1), and this complex along with adenine nucleotides forms the apoptosome and promotes procaspase-9. (springer.com)
  • 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)
  • The apoptosome is a large quaternary protein structure formed in the process of apoptosis. (wikipedia.org)
  • The term Apoptosome was first introduced in Yoshihide Tsujimoto's 1998 paper "Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? (wikipedia.org)
  • The apoptosome is a multimolecular holoenzyme complex assembled around the adaptor protein Apaf1 (apoptotic protease activating factor 1) upon mitochondria-mediated apoptosis which must be stimulated by some type of stress signal. (wikipedia.org)
  • The apoptosome triggers the activation of caspases in the intrinsic pathway of apoptosis. (wikipedia.org)
  • This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless sufficient numbers of apoptosomes are assembled within a particular time window, which would drive full-blown caspase activation and apoptosis. (sciencemag.org)
  • Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons. (nih.gov)
  • Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases in these neurons remains debated. (nih.gov)
  • We find that the ability of sympathetic neurons to undergo apoptosis in response to nerve growth factor (NGF) deprivation is completely dependent on having an intact apoptosome pathway. (nih.gov)
  • During stress-induced apoptosis, the initiator caspase-9 is activated by the Apaf-1 apoptosome and must remain bound to retain significant catalytic activity. (nih.gov)
  • This dysfunctional apoptosome activity was not correlated with any decrease of apoptosome component factors, but it was linked to an increased X-linked inhibitor of apoptosis protein (XIAP). (aacrjournals.org)
  • The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9. (uchicago.edu)
  • Here we show that DNA origami nanostructures provide a programmable molecular platform for the systematic analysis of signalling proteins by engineering a synthetic DNA origami-based version of the apoptosome, a multiprotein complex that regulates apoptosis by colocalizing multiple caspase-9 monomers. (mdrresearch.nl)
  • By contrast, in response to irreparable stress, HuR was reported to promote apoptosis through its association with protein ligand pp32/PHAPI, a potent activator of the apoptosome. (elsevier.com)
  • Kuwano, Y , Gallouzi, I & Gorospe, M 2010, Role of the RNA-binding protein HuR in apoptosis and apoptosome function . (elsevier.com)
  • Thus, we have identified a novel class of compounds that inhibits apoptosis by blocking the activation of the initiator caspase 9 by directly inhibiting the formation of the apoptosome complex. (ox.ac.uk)
  • Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. (rcsb.org)
  • Thus, these compounds provide a novel specific tool to investigate the role of the apoptosome in mitochondrion-dependent death paradigms. (ox.ac.uk)
  • Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. (rcsb.org)
  • The research team, led by Christopher W. Akey, PhD, BUSM professor of physiology & biophysics, determined the near atomic structure of the apoptosome using cryo-electron microscopy and were able to build a three-dimensional model. (eurekalert.org)
  • A cryo-electron microscopy model of the active human apoptosome illuminates how this "wheel of death" binds the protease procaspase-9 to initiate programmed cell death. (elifesciences.org)
  • Interestingly, caspase-8-cleaved caspase-9 induced lysosomal membrane permeabilization but failed to activate the effector caspases whereas apoptosome-dependent activation of caspase-9 could trigger both events. (ox.ac.uk)
  • Once formed, the apoptosome goes on to activate a group of proteins known as caspases. (scientificamerican.com)
  • hccs downregulation induces apoptosome-independent caspase-9 activation in mitochondriaA-C. TUNEL assays on st30 embryos co-injected with hccs-MO and Apaf1-MO (A), wt embryos exposed to staurosporine (B) and embryos injected with Apaf1-MO exposed to staurosporine (C) (n = 100/each treatment). (nih.gov)
  • These data clearly involve non-canonical, apoptosome-independent caspase-9 activation in the pathogenesis of microphthalmia. (nih.gov)
  • Cellular signaling in the programmed death pathway culminates in a complex assembly of proteins termed the "apoptosome. (eurekalert.org)
  • This multi-pronged pathway allows activation of procaspase-9 on the apoptosome and subsequent proteolytic activation of procaspase-3 and -7, which results in selective proteolysis of target proteins and cell death ( Bratton and Salvesen, 2010 ). (elifesciences.org)
  • However, the Apoptosome was known before this time as a ternary complex. (wikipedia.org)
  • The apoptosome was thought to be a mutimeric complex for two reasons. (wikipedia.org)
  • The wheel-shaped heptameric complex with sevenfold symmetry structure of the apoptosome was first revealed at 27 Å resolution by electron cryomicroscopy techniques and has a calculated mass of about 1 MDa (Acehan et al. (wikipedia.org)
  • In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. (sciencemag.org)
  • A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. (sciencemag.org)
  • Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. (sciencemag.org)
  • now use an electron microscope to reveal the three-dimensional structure of the active human apoptosome, in enough detail to determine the positions of many of the amino acids that make up the complex. (elifesciences.org)
  • The Apaf-1*procaspase-9 apoptosome complex functions as a proteolytic-based molecular timer. (nih.gov)
  • Indeed, procaspase-9 possessed higher affinity for the apoptosome and could displace the processed caspase-9 from the complex, thereby facilitating a continuous cycle of procaspase-9 recruitment/activation, processing, and release from the complex. (nih.gov)
  • Thus, the Apaf-1 apoptosome functions as a proteolytic-based 'molecular timer', wherein the intracellular concentration of procaspase-9 sets the overall duration of the timer, procaspase-9 autoprocessing activates the timer, and the rate at which the processed caspase-9 dissociates from the complex (and thus loses its capacity to activate procaspase-3) dictates how fast the timer 'ticks' over. (nih.gov)
  • Mouse Uaca (or nucling) is thought to interact with the Apaf1/pro-caspase-9 complex, thereby acting as a stabilizer for the apoptosome (Sakai T et al. (reactome.org)
  • In this Review, we discuss the complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response, and we highlight the similarities to another molecular signalling platform - the apoptosome - that monitors cellular health. (nature.com)
  • During activation an acentric disk is formed on the central hub of the apoptosome. (rcsb.org)
  • Apoptosome-independent activation of the lysosomal cell death pathway by caspase-9. (ox.ac.uk)
  • Adams, Cory: Apoptosomes: engines for caspase activation. (antikoerper-online.de)
  • My project was focused on understanding the mechanisms of caspase 9 processing and activation within the apoptosome. (mdanderson.org)
  • Energy levels, mitochondrial health and lysosomal compartmentalization are constantly under the surveillance of cellular health sensors such as the apoptosome and inflammasomes. (nature.com)
  • It is the core of the apoptosome, which is formed upon triggering of the mitochondrial apoptotic pathway. (biologists.org)
  • By using a large panel of genetically modified murine embryonic fibroblasts, we show here that, in response to tumor necrosis factor (TNF), caspase-8 cleaves and activates caspase-9 in an apoptosome-independent manner. (ox.ac.uk)
  • Apoptosomes bind to caspase-9 and activates it. (wikibooks.org)
  • Once the apoptosome was established as the procaspase-9 activator, mutations within this pathway became an important research area. (wikipedia.org)
  • The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic neurons with a markedly increased control over their apoptotic pathway. (nih.gov)
  • These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells. (rupress.org)
  • The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. (biologists.org)
  • 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)
  • The apoptosome binds and cleaves Procaspase-9 protein, releasing its mature, activated form. (wikipedia.org)
  • Apaf-1 oligomerizes into biologically active approximately 700-kDa and inactive approximately 1.4-MDa apoptosome complexes. (springer.com)
  • Neural cells can survive damage to the mitochondria if apoptosomes do not form. (redorbit.com)
  • When active the apoptosome is a dynamic molecular machine with three to five protease molecules tethered to it at any given time. (eurekalert.org)
  • A soluble protease is in turn cleaved and activated by the active apoptosome and this soluble protease then targets cellular components. (eurekalert.org)
  • Mouse Uaca, showing both cytoplasmic and perinuclear/nuclear localization, was suggested to translocate Apaf1-apoptosome to the nucleus after proapoptotic stress (Sakai T et al. (reactome.org)
  • According to the researchers the apoptosome is a wheel-like structure with seven spokes. (eurekalert.org)
  • The apoptosome is an extremely beautiful structure resembling a wheel with seven spokes. (scientificamerican.com)
  • We show herein that apoptosome-mediated cleavage of procaspase-9 occurs exclusively through a CARD-displacement mechanism, so that unlike the effector procaspase-3, procaspase-9 cannot be processed by the apoptosome as a typical substrate. (nih.gov)
  • The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. (sciencemag.org)
  • Caspase-9 autoprocessing displaces active caspase-9 bound to the apoptosome, thereby limiting proteolytic activity. (sciencemag.org)
  • Moreover, the defect in apoptosome activity in H460 cells was dramatically restored by the IAP-targeting SmacN7 peptide, which disrupted XIAP-caspase-9 binding, indicating an essential role of the IAP in the apoptosome inhibition. (aacrjournals.org)
  • Our results indicate that IAP-dependent suppression of apoptosome predominantly occurs in IAP-overexpressing tumor, and the IAP-targeting Smac peptide is an effective molecule to increase tumor cell death induced by chemotherapy in vitro and in vivo . (aacrjournals.org)
  • Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. (rupress.org)
  • In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). (rcsb.org)
  • This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. (rcsb.org)
  • Researchers from Boston University School of Medicine (BUSM) have for the first time mapped an active human apoptosome. (eurekalert.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)
  • Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. (wikipedia.org)
  • This oligomerization promotes the recruitment of caspase-9 (via its NH 2 -terminal prodomain) to the caspase recruitment domain (CARD) at the NH 2 terminus of Apaf-1, resulting in formation of the caspase-9-activating "apoptosome" ( 11 ). (aacrjournals.org)
  • There are hidden routes for cell death as well, which are independent of APAF-1 and therefore the apoptosome. (wikipedia.org)
  • The finding suggests that high neuroglobin levels may buffer neurons against the effect of this protein by preventing apoptosomes from forming. (redorbit.com)
  • This in turn will give a better understanding of how the apoptosome assembles and how the protein-cutting enzyme becomes activated. (elifesciences.org)
  • The apoptosome helps build an enzyme that degrades and eventually collapses the cell. (redorbit.com)
  • This disk forms a spiral that sits atop the central hub of the wheel-like apoptosome. (elifesciences.org)
  • B ) The initial velocities ( V 0 ) of apoptosome-bound C9-p35/p12, ProC9-TM, and C9-p35/p12-R56A on the substrate ProC3 were assessed by measuring caspase-3 DEVDase activity, as described in the Methods section. (nih.gov)
  • It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. (sciencemag.org)
  • However, the SmacN7 did not show any striking effect on the apoptosome activity of normal lung fibroblast cells, although these cells also expressed modest amounts of IAP. (aacrjournals.org)
  • The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may induce caspase-9 dimerization and subsequent autocatalysis. (wikipedia.org)