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.

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)

Apoptosomes are large protein complexes that play a crucial role in the process of programmed cell death, also known as apoptosis. They are formed when certain proteins in the cell, called caspases, are activated in response to signals indicating that the cell needs to die. The formation of apoptosomes leads to the activation of additional caspases, which then go on to break down various cellular structures and ultimately cause the cell to die.

Apoptosomes are composed of several proteins, including cytochrome c, Apaf-1 (apoptotic protease activating factor 1), and procaspase-9. When cytochrome c is released from the mitochondria into the cytoplasm, it binds to Apaf-1 and procaspase-9, leading to the formation of the apoptosome complex. This complex then cleaves and activates caspase-9, which in turn activates other caspases, setting off a chain reaction that results in apoptosis.

The formation of apoptosomes is an important mechanism for maintaining tissue homeostasis and getting rid of damaged or potentially harmful cells. Dysregulation of this process can contribute to the development of various diseases, including cancer and neurodegenerative disorders.

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 multimeric 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 ...
The binding of cyt c to Apaf-1 promotes apoptosome assembly, which in turn groups and activates caspase-9s. In the end, anti- ... This complex is called the apoptosome. Dark, just as Apaf-1, has an N-terminal CARD domain that interacts with caspase Dronc, ... On the other hand, it allows it to associate with Dark scaffold proteins to form a functional apoptosome and activate the DrICE ... Ubiquitylation of this residue of the CARD domain, which interacts with the apoptosome during apoptosis, keeps Dronc from ...
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 ...
... which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to ... Bratton SB, Salvesen GS (October 2010). "Regulation of the Apaf-1-caspase-9 apoptosome". Journal of Cell Science. 123 (Pt 19): ... February 2003). "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 ...
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- ...
Apoptosis is contingent upon ATP levels to form the energy dependent apoptosome. A distinct biochemical event only seen in ...
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 ...
... 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". ...
One hallmark of apoptosis is the release of cytochrome c, which then recruits Apaf-1 and dATP/ATP into an apoptosome complex. ... Hsp70 inhibits this process by blocking the recruitment of procaspase-9 to the Apaf-1/dATP/cytochrome c apoptosome complex. It ... August 2000). "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome". ...
"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 ...
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, ...
... which triggers the release of cytochrome c from the mitochondria and subsequent formation of the apoptosome, ultimately ...
... 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 BH3 interacting domain death agonist (BID) Caspases Cytochrome c Noxa Mitochondrion p53 upregulated ...
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 ...
Apoptosome Bcl-2 homologous antagonist killer (BAK) Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID ...
... 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 ...
... 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 multimeric 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 ...
Proximity-induced caspase-9 activation on a DNA origami-based synthetic apoptosome *Bas J. H. M. Rosier ...
Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome ... Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. DOI. Resolve DOI: ... Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. From National ...
Then, cytochrome c binds to apoptotic protease-activating factor-1 (APAF-1) and procaspase 9, forming the apoptosome complex, ... Chinnaiyan, A. M. The apoptosome: heart and soul of the cell death machine. Neoplasia 1, 5-15 (1999). ... assembly kinetics and activity of native Apaf-1 apoptosomes. EMBO J. 23, 2134-2145 (2004). ...
The apoptosome: signalling platform of cell death. SJ Riedl, GS Salvesen. Nature reviews Molecular cell biology 8 (5), 405-413 ...
"Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome," American Journal of Physiology. Cell ...
1 In Vitro Assembly and Analysis of the Apoptosome Complex. Claudia Langlais, Michelle A. Hughes, Kelvin Cain, and Marion ... Biochemical Analysis of Initiator Caspase-Activating Complexes: The Apoptosome and Death-Inducing Signaling Complex. Claudia ... Biochemical Analysis of Initiator Caspase-Activating Complexes: The Apoptosome and Death-Inducing Signaling Complex. ... apoptosome or ripoptosome formation, caspase activation, and cytochrome c release. Techniques are described for both in vitro ...
1 In Vitro Assembly and Analysis of the Apoptosome Complex. Claudia Langlais, Michelle A. Hughes, Kelvin Cain, and Marion ... Biochemical Analysis of Initiator Caspase-Activating Complexes: The Apoptosome and Death-Inducing Signaling Complex. Claudia ... Biochemical Analysis of Initiator Caspase-Activating Complexes: The Apoptosome and Death-Inducing Signaling Complex. ... apoptosome or ripoptosome formation, caspase activation, and cytochrome c release. Techniques are described for both in vitro ...
Kim HE, Du F, Fang M, Wang X. Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent ... Kim HE, Wang X. CAS and PHAPI Positively Regulate Apoptosome formation by Enhancing Nucleotide Exchange on Apaf-1. Mol. Cell ... specifically looking at the molecular mechanisms behind the activation mechanism of apoptosome. In the Dillin lab, I am ...
Next, cytochrome c binds to apoptotic protease activating factor-1 (Apaf-1) and leads to the assembly of the apoptosome complex ... Our research showed that 5-15 nm SiNPs activated caspase-9 and caspase-3. Subsequently, the apoptosome binds to caspase-9, and ...
Specific nitration of tyrosines 46 and 48 makes cytochrome c assemble a non-functional apoptosome. FEBS Letters. 2012. Vol: 586 ...
... to cellular stresses so lose membrane potential and mitochondrial proteins are released triggering formation of apoptosome ...
Cain K, Bratton SB and Cohen GM: The Apaf-1 apoptosome: A large caspase-activating complex. Biochimie. 84:203-214. 2002. View ... A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly. PLoS One. 6:e290582011. View ...
This redox mechanism of cyt c is realized earlier than its other well-recognized functions in the formation of apoptosomes and ... by interacting with several proteins and forming apoptosomes. Recently, two additional essential functions of cyt c in ...
... caspase-9 is activated through the apoptosome [97]. Among the effector caspases, the activation of caspase-3 is responsible for ...
... pro-caspase-9 binds to Apaf-1 oligomers and leads to the formation of the apoptosome, followed by caspase-3 activation[55-57]. ...
... which together with apoptotic protease activating factor 1 forms the apoptosome that activates caspase-9. Communication between ...
... from the apoptosome, a heptameric caspase activation organic (2, 3). The apoptosome activates and recruits caspase-9, an ...
Upon cytosolic entry, it serves as a cofactor in the formation of the "apoptosome," a complex consisting of the adaptor protein ...
... among which the cytochrome c is leading to the formation of the apoptosome, activation of caspase 9, and ultimately to the ...
Apoptosomes Entry term(s):. Apoptosomal Protein Complex. Apoptosome. Complex, Apoptosomal Protein. Protein Complex, Apoptosomal ... Apoptosomes - Preferred Concept UI. M0493498. Scope note. Multimeric protein complexes formed in the CYTOSOL that play a role ... The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9. ... The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.. ...
11/16/16 , A near-atomic structure of the dark apoptosome provides insight into assembly and activation. Cheng TC, Akey IV, ... We then built a nearly complete model of the apoptosome that includes 7- and 8-blade β-propellers. We find that the preference ... This wider spacing may be responsible for the lack of cytochrome c binding to β-propellers in the Dark apoptosome. Our ... Interestingly, β-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in ...
Apoptosomes Apoptosomes make life or death decisions in cells. Beta-secretase Beta-secretase trims proteins in the cell and ...
Apoptosome / Caspase. While many molecular machines keep a cell alive, there are even machines that are programmed to cause ... Guy S. Salvesen and Martin Renatus, "Apoptosome: The Seven-Spoked Death Machine," Developmental Cell, Vol. 2(3): 256-257 (March ... called the apoptosome,86 a molecular machine which receives signals indicating cellular stress and then initiates cell death, ...
Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature ... Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature ...
... required for the formation of the Apaf-1 apoptosome and therefore caspase activation. Conversely, the pro-apoptotic Bcl-2 ...
Expression of apoptosome-related genes in periodontitis , Article Gene Reports ; Volume 23 , 2021 ; 24520144 (ISSN) Gholami, L ... We examined expression of four apoptosome related genes namely CPSF7, AGO2, WDR33 and HUR1 in the blood and tissues of patients ...
Moreover, Aven co-localizes with the activated Apaf-1/Caspase-9 complex suggesting that it is a component of the apoptosome. ... This protein complex assembly called apoptosome leads to the activation of Casp-9 which then initiates or amplifies the ... Moreover, Aven co-localizes with the activated Apaf-1/Caspase-9 complex suggesting that it is a component of the apoptosome. ... This protein complex assembly called "apoptosome" leads to the activation of Casp-9 which then initiates or amplifies the ...
  • Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. (wikipedia.org)
  • This redox mechanism of cyt c is realized earlier than its other well-recognized functions in the formation of apoptosomes and caspase activation. (cdc.gov)
  • 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)
  • from the apoptosome, a heptameric caspase activation organic (2, 3). (woofahs.com)
  • Upon cytosolic entry, it serves as a cofactor in the formation of the "apoptosome," a complex consisting of the adaptor protein Apaf-1 and procaspase-9, which in turn causes the activation of caspase-9 and downstream caspases, such as caspase-3 ( Chinnaiyan, 1999 ). (rupress.org)
  • The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9. (bvsalud.org)
  • This protein complex assembly called "apoptosome" leads to the activation of Casp-9 which then initiates or amplifies the caspase cascade. (uni-frankfurt.de)
  • Moreover, Aven co-localizes with the activated Apaf-1/Caspase-9 complex suggesting that it is a component of the apoptosome. (uni-frankfurt.de)
  • This pathway most probably operates through the apoptosome complex because caspase 9 mutant mice suffered similar defects. (biologists.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)
  • There, I studied a mitochondria-initiated apoptosis pathway, specifically looking at the molecular mechanisms behind the activation mechanism of apoptosome. (berkeley.edu)
  • Since the (re)discovery of cytochrome c (cyt c) in the early 1920s and subsequent detailed characterization of its structure and function in mitochondrial electron transport, it took over 70 years to realize that cyt c plays a different, not less universal role in programmed cell death, apoptosis, by interacting with several proteins and forming apoptosomes. (cdc.gov)
  • Complejos proteicos multiméricos que se forman en el CITOSOL e intervienen en la activación de la APOPTOSIS. (bvsalud.org)
  • In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of an apoptosome. (wikipedia.org)
  • An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. (wikipedia.org)
  • The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic transmission electron microscopy in 2002, revealing a heptameric wheel-like particle with 7-fold symmetry. (wikipedia.org)
  • Recently, a medium resolution (9.5 Ångström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. (wikipedia.org)
  • The stable APAF-1 and cytochrome multimeric 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)
  • Kim HE , Du F, Fang M, Wang X. Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. (berkeley.edu)
  • GSDME-N terminal domain also permeabilizes the mitochondrial membrane, releasing cytochrome C and activating the apoptosome. (adipogen.com)
  • Additionally, interaction with HSP70 prevents the recruitment of APAF-1 and procaspase-9 to the apoptosome. (biomedcentral.com)
  • Negative regulation of the Apaf-1 apoptosome by Hsp70. (jefferson.edu)
  • However, the Apoptosome was known before this time as a ternary complex. (wikipedia.org)
  • The apoptosome was thought to be a multimeric 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)
  • Kim HE , Wang X. CAS and PHAPI Positively Regulate Apoptosome formation by Enhancing Nucleotide Exchange on Apaf-1. (berkeley.edu)
  • Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. (jefferson.edu)
  • Because the resolution of the apoptosome structure was relatively low, two controversial models for apoptosome assembly were proposed. (wikipedia.org)
  • ER stress is unique in releasing a sequestered caspase (caspase 12) that intercalates downstream of mitochondria to activate caspase 9 directly independent of the apoptosome. (medscape.com)
  • 11. Pro-apoptotic proteins released from the mitochondria regulate the protein composition and caspase-processing activity of the native Apaf-1/caspase-9 apoptosome complex. (nih.gov)
  • In this pathway, cytochrome c released from mitochondria facilitates the formation of an Apaf-1 apoptosome that recruits and activates caspase-9. (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)
  • Further evidence that caspase activation occurs upstream of the mitochondria and that the apoptosome functions to amplify the caspase cascade was presented by Vanessa Marsden (The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia). (biomedcentral.com)
  • doi: ten.1101/cshperspect.a008706 Cite this short article as Cold Spring Harb Perspect Biol 2013;five:aS.W.G. Tait and D.R. GreenBax/Bak-induced mitochondrial outer membrane permeabilizationCytochrome c Apaf-1 monomers Smac and Omi Procaspase-Mitochondria- Loss of mitochondrial funcion Apoptosome formation XIAP - Release of toxic mitochondrial proteins Caspase-3/7 activation Caspase-9 recruitment and activation Caspaseindependent cell deathApoptosisFigure 1. (axlinhibitor.com)
  • 3. Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. (nih.gov)
  • This arrangement was not described before in other SAM proteins, but is reminiscent of the apoptosome and inflammasome - well known apoptotic ring-like oligomers. (opatowskylab.com)
  • Upon loss of the mitochondrial membrane potential, apoptosome activation led to caspase-9 processing, activation of caspase-3-like caspases, and poly (ADP-ribose) polymerase cleavage. (nih.gov)
  • 2. Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. (nih.gov)
  • The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. (nih.gov)
  • Once the apoptosome was established as the procaspase-9 activator, mutations within this pathway became an important research area. (wikipedia.org)
  • Procaspase-9 is recruited to heptameric Apaf-1 complexes forming the apoptosome. (axlinhibitor.com)
  • Our data are consistent with a model where caspase-2 activation occurs by oligomerization, independent of the Apaf-1 apoptosome. (rupress.org)
  • There are hidden routes for cell death as well, which are independent of APAF-1 and therefore the apoptosome. (wikipedia.org)