File Hapop.jpg thumb alt 3D structure of the human apoptosome CARD complex. 3D structure of the human apoptosome CARD complex. p blue apoptosome platform magenta CARD disk p p Yuan et al. 2010, Structure of an apoptosome procaspase 9 CARD complex ref name Yuan Yuan S, Yu X, Topf M, Ludtke SJ, Wang X, Akey CW. http www.cell.com structure retrieve pii S0969212610001346 Structure of an apoptosome procaspase 9 CARD complex. Structure. 2010 May 18 5 571 83. ref p The apoptosome is a large quaternary protein ..., it binds to the cytosolic protein Apaf 1 to facilitate the formation of apoptosome. An early biochemical study suggests a two to one ratio of cytochrome c to apaf 1 for apoptosome formation ... 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 nanometer nm resolution by cryogenic ..., Akey CW Three dimensional structure of the apoptosome implications for assembly, procaspase 9 binding .... Recently, a medium resolution 9.5 ngstr m structure of human apoptosome was also solved by cryo ... CARD, NBARC and WD40 and cytochrome c. ref name Yuan Once formed, the apoptosome can then recruit ... effector caspases and trigger a cascade of events leading to apoptosis. History The term Apoptosome ... in Apoptosis Apoptosomes or Mitochondria? Genes to Cells 3.11 1998 697 707. ref However, the Apoptosome .... Journal of Biological Chemistry 273 1998 33489 3494 ref The criteria for an apoptosome were ... complex fit this description, 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 ... c would not result in apoptosis. ref name Zou Once the apoptosome was established as the procaspase ..., which are independent of APAF 1 and therefore the apoptosome. These routes are also independent ... 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
title A novel enhancer of the Apaf1 apoptosome involved in cytochrome c dependent caspase activation ... L, Robbins P D, Alnemri E S year 2000 month August title Negative regulation of the Apaf 1 apoptosome ... c multimeric complex is a functional apoptosome that activates procaspase 9. journal J. Biol. Chem. volume ... 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 cell membranes, 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 ... 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 ref cite pmid 16380419 ref . 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, Richard Lounsbery Award , from the National Academy of Sciences, USA 2006, Shaw Prize , from the Shaw Foundation References reflist 1 Shaw Prize Persondata Metadata see Wikipedia Persondata . NAME Wang Xiaodong ALTERNATIVE NAMES SHORT DESCRIPTION American biochemist DATE OF BIRTH PLACE OF BIRTH DATE OF DEATH PLACE OF DEATH DEFAULTSORT Wang Xiaodong Category Livi ... more details
factor receptor TNF receptor , which can activate caspase 8 and 10 the apoptosome regulated by cytochrome ... 1 ref See also apoptosis apoptosome bcl 2 metacaspase paracaspase pyroptosis The Proteolysis Map ... more details
apoptosome involved in cytochrome c dependent caspase activation and apoptosis journal J ... apoptosome involved in cytochrome c dependent caspase activation and apoptosis. journal J. Biol. Chem ... 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 .... ref name h460 cite journal author Yang L, Mashima T, Sato S title Predominant suppression of apoptosome ... 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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