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Autoactivation Of Procaspase-9 By Apaf-1-mediated Oligomerization.

S. Srinivasula, M. Ahmad, T. Fernandes-Alnemri, E. Alnemri
Published 1998 · Biology, Medicine

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Activation of procaspase-9 by Apaf-1 in the cytochrome c/dATP-dependent pathway requires proteolytic cleavage to generate the mature caspase molecule. To elucidate the mechanism of activation of procaspase-9 by Apaf-1, we designed an in vitro Apaf-1-procaspase-9 activation system using recombinant components. Here, we show that deletion of the Apaf-1 WD-40 repeats makes Apaf-1 constitutively active and capable of processing procaspase-9 independent of cytochrome c an dATP. Apaf-1-mediated processing of procaspase-9 occurs at Asp-315 by an intrinsic autocatalytic activity of procaspase-9 itself. We provide evidence that Apaf-1 can form oligomers and may facilitate procaspase-9 autoactivation by oligomerizing its precursor molecules. Once activated, caspase-9 can initiate a caspase cascade involving the downstream executioners caspase-3, -6, and -7.
This paper references
10.1016/S0960-9822(06)00120-5
CED-4 induces chromatin condensation in Schizosaccharomyces pombe and is inhibited by direct physical association with CED-9
C. James (1997)
10.1073/PNAS.93.25.14486
Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases.
S. Srinivasula (1996)
10.1016/S0968-0004(97)01043-8
The CARD domain: a new apoptotic signalling motif.
K. Hofmann (1997)
The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death.
J. Yuan (1992)
10.1002/BIES.950190609
Death substrates come alive
A. Porter (1997)
10.1074/JBC.273.5.2926
An Induced Proximity Model for Caspase-8 Activation*
M. Muzio (1998)
10.1042/BJ3260001
Caspases: the executioners of apoptosis.
G. Cohen (1997)
10.1126/SCIENCE.275.5303.1122
Interaction of CED-4 with CED-3 and CED-9: A Molecular Framework for Cell Death
A. Chinnaiyan (1997)
10.1016/0092-8674(95)90071-3
FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis
A. Chinnaiyan (1995)
10.1016/S0092-8674(00)80501-2
Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
H. Zou (1997)
10.1074/jbc.272.48.30299
Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c
F. Li (1997)
CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP.
M. Ahmad (1997)
10.1016/0092-8674(95)90422-0
Protease activation during apoptosis: Death by a thousand cuts?
S. Martin (1995)
10.1074/JBC.271.43.27099
The Ced-3/Interleukin 1β Converting Enzyme-like Homolog Mch6 and the Lamin-cleaving Enzyme Mch2α Are Substrates for the Apoptotic Mediator CPP32*
S. Srinivasula (1996)
10.1016/S0092-8674(00)81334-3
Human ICE/CED-3 Protease Nomenclature
E. Alnemri (1996)
10.1016/S0968-0004(97)01085-2
Caspases: killer proteases.
D. Nicholson (1997)
10.1002/j.1460-2075.1995.tb07184.x
Interleukin‐1 beta converting enzyme requires oligomerization for activity of processed forms in vivo.
Y. Gu (1995)
10.1016/S0092-8674(00)81005-3
A License to Kill
A. Fraser (1996)
10.1038/385653A0
Interaction between the C. elegans cell-death regulators CED-9 and CED-4
M. Spector (1997)
10.1038/41913
Role of CED-4 in the activation of CED-3
A. Chinnaiyan (1997)
10.1126/SCIENCE.275.5303.1126
Interaction and Regulation of Subcellular Localization of CED-4 by CED-9
D. Wu (1997)
10.1074/jbc.272.30.18542
FLAME-1, a Novel FADD-like Anti-apoptotic Molecule That Regulates Fas/TNFR1-induced Apoptosis*
S. Srinivasula (1997)
10.1074/jbc.273.10.5841
Caspase-9, Bcl-XL, and Apaf-1 Form a Ternary Complex*
G. Pan (1998)
10.1074/jbc.272.41.25417
Identification and Molecular Cloning of Two Novel Receptors for the Cytotoxic Ligand TRAIL*
M. Macfarlane (1997)
10.1038/40901
X-linked IAP is a direct inhibitor of cell-death proteases
Q. Deveraux (1997)
10.1016/S0092-8674(00)80434-1
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li (1997)
10.1074/JBC.273.14.7783
Blk, a BH3-containing Mouse Protein That Interacts with Bcl-2 and Bcl-xL, Is a Potent Death Agonist*
R. Hegde (1998)
10.1073/PNAS.93.15.7464
In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.
T. Fernandes-Alnemri (1996)
10.1002/j.1460-2075.1995.tb00245.x
Cytotoxicity‐dependent APO‐1 (Fas/CD95)‐associated proteins form a death‐inducing signaling complex (DISC) with the receptor.
F. Kischkel (1995)
10.1016/S0092-8674(00)80430-4
Caspases: Intracellular Signaling by Proteolysis
G. Salvesen (1997)
10.1016/S0092-8674(00)81265-9
Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death
M. Boldin (1996)
10.1074/JBC.270.14.7795
A Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain (*)
M. Boldin (1995)
10.1016/S1074-7613(00)80428-8
ICE family proteases: mediators of all apoptotic cell death?
P. Henkart (1996)
10.1016/S0960-9822(06)00216-8
Caenorhabditis elegans CED-4 stimulates CED-3 processing and CED-3-induced
S. Seshagiri (1997)
10.1093/emboj/17.8.2215
IAPs block apoptotic events induced by caspase‐8 and cytochrome c by direct inhibition of distinct caspases
Q. Deveraux (1998)
10.1016/S1097-2765(00)80032-5
Autoproteolytic activation of pro-caspases by oligomerization.
X. Yang (1998)
10.1016/S0092-8674(00)81874-7
Apoptosis by Death Factor
S. Nagata (1997)
10.1016/S0092-8674(00)81266-0
FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex
M. Muzio (1996)
10.1038/385086A0
RAIDD is a new 'death' adaptor molecule
H. Duan (1997)



This paper is referenced by
Apaf-1 Caspase-1-activating Protein Related to Identification of Ipaf, a Human TRANSDUCTION: MECHANISMS OF SIGNAL
Emad S. Alnemri (2014)
Apo-2 L / TRAIL ( BMS 247550 ) and − peptide potentiates epothilone B derivative caspases ( Smac / DIABLO ) or cotreatment with N-terminus of Smac / DIABLO Ectopic overexpression of second mitochondria-derived activator
Erica O'Bryan (2002)
Regulation and functional significance of ATP binding cassette transporters in human placenta.
Denis Evseenko (2008)
Proteína de choque térmico de 60kDa de klebsiella pneumoniae y especies reactivas de oxígeno en la apoptosis inducida con ácido ursólico en células MRC-5
Jaret Sánchez Cabrera (2018)
10.14279/DEPOSITONCE-164
Mechanisms of Apoptosis in Cancer: Regulatory Role of Caspases
F. Essmann (2000)
10.1042/BST0360001
Caspase activation cascades in apoptosis.
S. Logue (2008)
10.1097/01.WCB.0000080702.47016.FF
Interaction between XIAP and Smac/DIABLO in the Mouse Brain after Transient Focal Cerebral Ischemia
A. Saito (2003)
10.4049/jimmunol.167.2.733
B Cell Receptor Cross-Linking Triggers a Caspase-8- Dependent Apoptotic Pathway That Is Independent of the Death Effector Domain of Fas-Associated Death Domain Protein1
L. Besnault (2001)
10.1128/MCB.21.9.3001-3011.2001
Two Distinct Domains within CIITA Mediate Self-Association: Involvement of the GTP-Binding and Leucine-Rich Repeat Domains
M. Linhoff (2001)
10.1091/mbc.E07-09-0858
Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis.
Elisabetta Ferraro (2008)
1National Cancer Institute, NIH. Research Associates and Howard Temin Award CA-78534 from Supported in part by a grant from the Ohio Cancer Cells 1 a Caspase-9-dependent Pathway in SH-SY5Y Neuroblastoma p53 Mediates DNA Damaging Drug-induced Apoptosis through
Hongjuan Cui (2013)
10.1254/JPHS.10217SC
Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells.
A. Yamamuro (2011)
10.1074/JBC.M108530200
Anti-apoptotic activity of the free card domain of procaspase-9: A novel endogenous rescue pathway
A. Stephanou (2002)
10.7275/JR9N-GZ79
Regulation of Caspase-9 by Natural and Synthetic Inhibitors
Kristen L. Huber (2012)
10.1182/BLOOD.V98.9.2828
Sphingosine 1-phosphate antagonizes apoptosis of human leukemia cells by inhibiting release of cytochrome c and Smac/DIABLO from mitochondria.
O. Cuvillier (2001)
10.3390/pharmaceutics12090894
Can Implementation of Genetics and Pharmacogenomics Improve Treatment of Chronic Low Back Pain?
Vladislav Suntsov (2020)
Microbial pathogen-induced necrosis mediated by NLRP3 and ASC
S. Willingham (2007)
Characterization of new chemosensitizing agents
L. Schyschka (2009)
10.1038/ncomms13565
The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities
C. Wu (2016)
10.1002/9781119432463.CH2
Mitochondria in focus: Targeting the cell-death mechanism
H. Vitto (2018)
10.1007/s10534-007-9089-4
Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo
Francisco Carvallo-Chaigneau (2007)
10.1038/cdd.2017.44
Caspases and their substrates
O. Julien (2017)
10.1111/j.1749-6632.2000.tb05595.x
Apoptosis as a Scaffold for Building up the B Cell Repertoire
A. Bras (2000)
10.1002/mnfr.200900260
Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway.
M. Seon (2010)
10.1177/153537020322800602
Asbestos-Induced Pulmonary Toxicity: Role of DNA Damage and Apoptosis
D. Upadhyay (2003)
10.1016/S0300-9084(02)01376-7
The Apaf-1 apoptosome: a large caspase-activating complex.
K. Cain (2002)
10.1016/S1368-8375(02)00116-1
Cisplatin induces apoptosis in oral squamous carcinoma cells by the mitochondria-mediated but not the NF-kappaB-suppressed pathway.
M. Azuma (2003)
10.1038/88684
A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins
T. Miyazaki (2001)
10.1152/AJPCELL.00331.2005
Subcellular localization of Apaf-1 in apoptotic rat pituitary cells.
M. Potokar (2006)
10.1016/S0079-6468(08)70068-7
Caspase inhibitors as anti-inflammatory and antiapoptotic agents.
Piotr P. Graczyk (2002)
10.1016/S0959-440X(00)00146-9
Caspases: key players in programmed cell death.
M. Gruetter (2000)
10.1093/emboj/19.16.4310
Negative regulation of cytochrome c‐mediated oligomerization of Apaf‐1 and activation of procaspase‐9 by heat shock protein 90
P. Pandey (2000)
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