The apoptosome is a large quaternary protein structure formed in the process of apoptosis . Its formation ... the formation of apoptosome. An early biochemical study suggests a two to one ratio of cytochrome c to apaf 1 for apoptosome formation. However, recent structural studies suggest the cytochrome c to apaf ... as third component binds to apaf 1, however its exact role is still debated. The mammalian apoptosome had never been crystallized, but a human APAF 1 cytochrome c apoptosome has been imaged at lower 2 ... X, Morgan DG, Heuser JE, Wang X, Akey CW Three dimensional structure of the apoptosome implications ... of human apoptosome was also solved by cryo electron microscopy , which allows unambiguous inference ... of an apoptosome procaspase 9 CARD complex. Structure. 2010 May 18 5 571 83. ref . Once formed, the apoptosome .... History The term Apoptosome was first introduced in Yoshihide Tsujimoto s 1998 paper Role of Bcl ... to Cells 3.11 1998 697 707. ref However, the Apoptosome was known before this time as a ternary ternary ... Chemistry 273 1998 33489 3494 ref The criteria for an apoptosome were laid out in 1999. Firstly ..., and is now called the apoptosome. ref name Zou Zou, Li, Liu and Wang. An APAF 1z Cytochrome c Multimeric Complex Is a Functional Apoptosome That Activates Procaspase 9. Journal Biological Cemistry, 274 17 1999 11549 11556. ref The apoptosome was thought to be a Oligomer mutimeric complex ... cytochrome c would not result in apoptosis. ref name Zou Once the apoptosome was established as the procaspase ... routes for cell death as well, which are independent of APAF 1 and therefore the apoptosome. These routes ... prove useful with further research. ref Belmokhtar, C.A. et al. Apoptosome independent Pathway for Apoptosis. Journal of Biological Chemistry 278 2003 29571 9580. ref Structure The apoptosome is a multimolecular ... be stimulated by some type of stress signal T formation of the apoptosome requires the presence of Adenosine ... Ceconi F., Ferraro E., Fuoco C., Strappazzon F. Apoptosome structure and regulation. Online . http ... more details
orphan date April 2010 Apoptosis is a programmed form of cell death involving the degradation of cellular constituents by a group of cysteine proteases called caspase s. The caspases can be activated through either the intrinsic mitochondrial mediated or extrinsic death receptor mediated apoptotic pathways. The intrinsic apoptotic pathway is characterized by permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm . Cytochrome c then forms a multi protein complex known as the apoptosome and initiates activation of the caspase cascade through caspase 9. The extrinsic apoptotic pathway is activated by death receptors on the plasma membrane such as tumour necrosis factor receptor 1 TNFR1 and Fas CD95 . As ligand s bind to these receptors, the death inducing signaling complex DISC is formed leading to initiation of the caspase cascade through caspase 8. References Danial, N.N., and Korsmeyer, S.J. 2004 . Cell death critical control points. Cell 116, 205 219. Kroemer, G., Galluzzi, L., and Brenner, C. 2007 . Mitochondrial membrane permeabilization in cell death. Physiol Rev 87, 99 163. Taylor, R.C., Cullen, S.P., and Martin, S.J. 2008 . Apoptosis controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9, 231 241. Category Apoptosis ... more details
Guy Salvesen is a South African born biochemist , best known for his work in the field of apoptosis . His research focuses on protease s and their Protease inhibitor biology inhibitors in humans, with particular emphasis on the caspase s of the apoptotic cell death pathway. His PhD in biochemistry is from the University of Cambridge , studying under Alan Barrett biochemist Alan Barrett 1981 . His first posts were at the Strangeways Laboratory and Medical Research Council UK MRC Laboratory of Molecular Biology in Cambridge . In 1985, Salvesen moved to the USA, taking up a position at the University of Georgia . He joined the faculty of Duke University in 1987, and moved his laboratory to the Sanford Burnham Institute for Medical Research , La Jolla , California in 1996. As of 2007, Salvesen is the Program Director in Apoptosis and Cell Death Research at the Sanford Burnham Institute. He also holds an Assistant Professorship at Duke University. He serves as the Vice Chair the Americas of the Biochemical Journal . Key recent publications Pop C, Timmer J, Sperandio S, Salvesen GS. 2006 The apoptosome activates caspase 9 by dimerization. Mol Cell 22 269 275 Eckelman BP, Salvesen GS. 2006 The human anti apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281 3254 3260 Pop C, Salvesen GS. 2005 The nematode death machine in 3D. Cell 123 192 193 Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS. 2005 XIAP inhibits caspase 3 and 7 using two binding sites evolutionarily conserved mechanism of IAPs. EMBO J 24 645 655 Drag, M., Mikolajczyk, J., Krishnakumar, I. M., Huang, Z. and Salvesen, G. S. 2008 Activity profiling of human deSUMOylating enzymes SENPs with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family. Biochem J 409, 461 469 Riedl, S. J. and Salvesen, G. S. 2007 The apoptosome signalling platform of cell death. Nat Rev Mol Cell Biol 5, 405 413 Mikolajczyk, J., Drag, M., Bekes, ... more details
protein Name BCL2 binding component 3 caption image width HGNCid 17868 Symbol BBC3 AltSymbols JFY1, PUMA EntrezGene 27113 OMIM 605854 RefSeq NM 014417 UniProt PDB ECnumber Chromosome 19 Arm q Band 13.3 LocusSupplementaryData 13.4 The p53 upregulated modulator of apoptosis , or PUMA, is a pro apoptosis apoptotic member of the Bcl 2 protein family. ref name pmid11463392 cite journal author Nakano K, Vousden KH title PUMA, a novel proapoptotic gene, is induced by p53 journal Mol. Cell volume 7 issue 3 pages 683 94 year 2001 month March pmid 11463392 doi 10.1016 S1097 2765 01 00214 3 url ref ref name pmid11572983 cite journal author Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T title Expression of bbc3, a pro apoptotic BH3 only gene, is regulated by diverse cell death and survival signals journal Proc. Natl. Acad. Sci. U.S.A. volume 98 issue 20 pages 11318 23 year 2001 month September pmid 11572983 pmc 58727 doi 10.1073 pnas.201208798 url ref Bcl 2 family members can form hetero or homodimers, and they act as anti or pro apoptosis apoptotic regulators that are involved in a wide variety of cellular activities. The expression of PUMA is regulated by the tumor suppressor p53 , and PUMA has been shown to be involved in p53 mediated apoptosis. See also Apoptosis Apoptosome Bcl 2 Bcl 2 associated X protein BAX BH3 interacting domain death agonist BID Caspases Cytochrome c Noxa Mitochondrion References Reflist gene 19 stub Category Apoptosis Category Programmed cell death Category Proteins ... more details
Xiaodong Wang zh s t p W ng Xi od ng , born 1963 is an United States American biochemist best known for his work with cytochrome c . His laboratory developed an in vitro assay for the activation of the apoptosis related proteinase Caspase 3. This allowed the biochemical purification a complex of Cytochrome c, Caspase 9 and the Apoptotic Protease Activating factor 1 Apaf 1 . These components are essential for forming a ternary complex called the apoptosome that activates Caspase 3 downstream of the intracellular or mitochondrial pathway of apoptosis. ref cite web url http www.cell.com abstract S0092 8674 00 80501 2 title Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf 1, a human protein homologous to C. elegans CED 4, participates in cytochrome c dependent activation of caspase 3.Cell. 1997 Aug 8 90 3 405 13. accessdate 2009 02 09 date 1997 08 08 ref He was awarded the 2006 Shaw Prize in Life Science and Medicine. ref cite web url http www.shawprize.org en laureates 2006 life Wang announcement.html title The Shaw Prize accessdate 2007 08 01 date 2006 06 21 work http www.shawprize.org The Shaw Prize ref Wang is a member of United States National Academy of Sciences and the Howard Hughes Medical Institute . Currently he is a professor at National Institute of Biological Sciences, Beijing . ref http www.nibs.ac.cn english ?act view&id 109 Xiaodong Wang, Ph.D. Lab Research Profile ref Honors & awards 2002, Hackerman Award, from the Welch Foundation 2001, Paul Marks Prize, from the Memorial Sloan Kettering Cancer Center 2000, Eli Lilly Award, from American Chemical Society 2007, Lounsbery Award Richard Lounsbery Award , from the National Academy of Sciences, USA 2006, Shaw Prize , from the Shaw Foundation References reflist 1 Shaw Prize DEFAULTSORT Wang Xiaodong Category Living people Category American biochemists zh ... more details
. title A novel enhancer of the Apaf1 apoptosome involved in cytochrome c dependent caspase activation ... 1 apoptosome by Hsp70 journal Nat. Cell Biol. volume 2 issue 8 pages 476 83 publisher location ENGLAND ... c multimeric complex is a functional apoptosome that activates procaspase 9. journal J. Biol ... more details
Granzymes are serine protease s that are released by cytoplasmic granules within cytotoxic T cell s and natural killer cell s. Their purpose is to induce apoptosis within virus infected cells, thus destroying them. ref name Bots 2006 cite journal author Bots M, Medema JP title Granzymes at a glance journal J. Cell. Sci. volume 119 issue Pt 24 pages 5011 4 year 2006 doi 10.1242 jcs.03239 pmid 17158907 ref Cytotoxic T cells and natural killer cells release a protein called perforin , which attacks the target cells. Researchers used to think that perforin creates pores within the cells, through which the granzymes can enter, inducing apoptosis. However, new evidence indicates that a multimeric complex GZMB Granzyme B , perforin, and granulysin can enter a cell through the mannose 6 phosphate receptor or another receptor found in tumor cells and is enclosed in a vesicle a sac . ref name Buzza 2006 cite journal author Buzza MS, Bird PI title Extracellular granzymes current perspectives journal Biol. Chem. volume 387 issue 7 pages 827 37 year 2006 pmid 16913832 doi 10.1515 BC.2006.106 ref Perforin then allows GrB to pass through the vesicle surface and into the cell, causing apoptosis by various pathways. They do so by cleaving caspase s especially caspase 3 , which in turn activates caspase activated DNase. This enzyme degrades DNA, thus inducing apoptotic cascades. Also, GrB cleaves the protein Bid, which recruits the protein Bax and Bak to change the membrane permeability of the mitochondria, causing the release of cytochrome c which is one of the parts needed to activate caspase 9 via the Apoptosome , Smac Diablo and Omi HtrA2 which suppress the inhibitor of apoptosis proteins IAPs , among other proteins. As well, GrB is shown to cleave many of the chemicals responsible for apoptosis without the aid of caspase, as proven by experiments on caspase knockout mice CTL cells incubated with other cells. Granzyme secretion can be detected and measured using Western Blot or E ... more details
apoptosis by preventing recruitment of procaspase 9 to the Apaf 1 apoptosome journal Nat. Cell Biol ... into an apoptosome complex. This complex then cleaves procaspase 9, activating caspase 9 and eventually ... of procaspase 9 to the Apaf 1 dATP cytochrome c apoptosome complex. It does not bind directly ... more details
caspase 8 and 10 the apoptosome regulated by cytochrome c and the bcl 2 Bcl 2 family , which ... pmid 17053807 ref See also apoptosis apoptosome bcl 2 metacaspase paracaspase pyroptosis ... more details
apoptosome involved in cytochrome c dependent caspase activation and apoptosis journal J ... journal author Chu ZL, Pio F, Xie Z, et al. title A novel enhancer of the Apaf1 apoptosome involved ... more details
PBB geneid 842 Caspase 9 is an initiator caspase , ref http www.nlm.nih.gov cgi mesh 2007 MB cgi?mode &term Caspase 9 Caspase 9 Bot generated title ref encoded by the CASP9 gene. CASP9 orthologs ref name OrthoMaM cite web title OrthoMaM phylogenetic marker CASP9 coding sequence url http www.orthomam.univ montp2.fr orthomam data cds detailMarkers ENSG00000132906 CASP9.xml ref have been identified in all mammals for which complete genome data are available. Unique orthologs are also present in lizards , lissamphibian s, and teleosts . The aspartic acid specific protease caspase 9 has been linked to the mitochondrial death pathway. It is activated during programmed cell death apoptosis . Induction of stress signaling pathways JNK SAPK causes release of cytochrome c from mitochondria and activation of apaf 1 apoptosome , which in turn cleaves the pro enzyme of caspase 9 into the active form. Once initiated caspase 9 goes on to cleave caspase 3 procaspase 3 & caspase 7 procaspase 7 , which cleave several cellular targets, including poly ADP ribose polymerase . Interactions Caspase 9 has been shown to Protein protein interaction interact with NLRP1 , ref name pmid11113115 cite journal last Chu first Z L authorlink coauthors Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed J C year 2001 month Mar. title A novel enhancer of the Apaf1 apoptosome involved in cytochrome c dependent caspase activation and apoptosis journal J. Biol. Chem. volume 276 issue 12 pages 9239 45 publisher location United States issn 0021 9258 pmid 11113115 doi 10.1074 jbc.M006309200 bibcode oclc id url language format accessdate laysummary laysource laydate quote ref ref name pmid11076957 cite journal last Hlaing first T authorlink coauthors Guo R F, Dilley K A, Loussia J M, Morrish T A, Shi M M, Vincenz C, Ward P A year 2001 month Mar. title Molecular cloning and characterization of DEFCAP L and S, two isoforms of a novel member of the mammalian Ced 4 family of apoptosis proteins journa ... more details
ATP , which then bind to pro caspase 9 to create a protein complex known as an apoptosome . The apoptosome ... suppression of apoptosome by inhibitor of apoptosis protein in non small cell lung cancer H460 cells ... more details
caspase 9, and initiates apoptosis without the formation of an apoptosome or cytochrome c release. This implies that DCC regulates a novel pathway for caspase activation, and that it is one that is apoptosome ... more details
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