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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining

◀ Back to CASP9

APAF1 — CASP9

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Srinivasula et al., Cancer Res 1999 : It can also block activation of caspase-9 and -3 by Apaf-1 in an in vitro cytochrome c-dependent caspase activation assay
Hu et al., EMBO J 1999 : Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1 mediated caspase-9 activation and apoptosis
Cain et al., J Biol Chem 1999 : In mammals, apoptotic protease activating factor 1 ( Apaf-1 ), cytochrome c, and dATP activate caspase-9 , which initiates the postmitochondrial mediated caspase cascade by proteolytic cleavage/activation of effector caspases to form active approximately 60-kDa heterotetramers
Zhou et al., Proc Natl Acad Sci U S A 1999 : Direct recruitment and activation of caspase-9 by Apaf-1 through the homophilic CARD/CARD ( Caspase Recruitment Domain ) interaction is critical for the activation of caspases downstream of mitochondrial damage in apoptosis
Rodriguez et al., Genes Dev 1999 : Activation of caspase-9 , which mediates oncogene and drug induced apoptosis, requires binding to the protein APAF-1
Genini et al., J Biol Chem 2000 (Leukemia, Lymphocytic, Chronic, B-Cell) : In contrast to dADP, both ADP and its nonhydrolyzable alpha, beta-methylphosphonate analog were strong inhibitors of APAF-1 dependent caspase activation ... These results suggest that the potency of adenine deoxynucleotides as co-factors for APAF-1 dependent caspase activation is due both to stimulation by the 5'-triphosphates and lack of inhibition by the 5'-diphosphates
Cain et al., J Biol Chem 2000 : Oligomerization of Apaf-1 , in the presence of dATP and cytochrome c, is required for the activation of caspase-9 and produces a caspase activating apoptosome complex
Jaroszewski et al., Proteins 2000 : This prediction suggests a detailed molecular mechanism for the `` induced proximity '' hypothesis ( Salvesen and Dixit, Proc Natl Acad Sci USA 1999 ; 96 : 10964-10967 ) for CED3/caspase-9 activation by CED4/APAF-1 complex
Perkins et al., Cancer Res 2000 : This conclusion is supported by the observation that in HL-60/Apaf-1 cells, ectopic expression of dominant negative caspase-9, its inhibitory short isoform caspase-9b, or XIAP or treatment with the caspase inhibitor zVAD ( 50 microM ) inhibited Apaf-1 induced caspase-8 and Bid cleavage, mitochondrial deltapsim, release of cyt c, and apoptosis
von Ahsen et al., J Cell Biol 2000 : Proapoptotic members of the Bcl-2 protein family, including Bid and Bax, can activate apoptosis by directly interacting with mitochondria to cause cytochrome c translocation from the intermembrane space into the cytoplasm, thereby triggering Apaf-1 mediated caspase activation
Purring-Koch et al., Proc Natl Acad Sci U S A 2000 : In the apoptosis pathway in mammals, cytochrome c and dATP are critical cofactors in the activation of caspase 9 by Apaf-1
Seol et al., Int J Oncol 2001 (Carcinoma, Squamous Cell...) : These results suggest that apoptosis of PCI-1 cells by As2O3 is induced by activation of caspase-3 via cytochrome c, caspase-9 and Apaf-1 complex
Fu et al., Biochem Biophys Res Commun 2001 : Apaf-1 plays a crucial role in the cytochrome c/dATP dependent activation of caspase-9 and -3
Chipuk et al., J Biol Chem 2001 : Bcl-xL blocks transforming growth factor-beta 1-induced apoptosis by inhibiting cytochrome c release and not by directly antagonizing Apaf-1 dependent caspase activation in prostate epithelial cells
Lauber et al., J Biol Chem 2001 : Here, we report that different apoptotic stimuli induced the caspase mediated cleavage of Apaf-1 into an 84-kDa fragment
Pathan et al., J Biol Chem 2001 (Neoplasms) : TUCAN interferes with binding of Apaf1 to procaspase-9 and suppresses caspase activation induced by the Apaf1 activator, cytochrome c. Overexpression of TUCAN in cells by stable or transient transfection inhibits apoptosis and caspase activation induced by Apaf1/caspase-9 dependent stimuli, including Bax, VP16, and staurosporine, but not by Apaf1/caspase-9 independent stimuli, Fas and granzyme B
Wolf et al., J Biol Chem 2001 (Ovarian Neoplasms) : Defective cytochrome c-dependent caspase activation in ovarian cancer cell lines due to diminished or absent apoptotic protease activating factor-1 activity
Concannon et al., Gene Expr 2001 : Mitochondrial cytochrome c release in response to pro-apoptotic signals leads to the formation of a cytochrome c/Apaf-1/procaspase-9 complex ( the apoptosome ) and resultant activation of caspase-9 and caspase-3
Cain et al., J Biol Chem 2001 : Using a defined apoptosome reconstitution system with recombinant Apaf-1 and cytochrome c, K ( + ) also inhibits caspase activation by abrogating Apaf-1 oligomerization and apoptosome assembly
Reimertz et al., J Neurochem 2001 (Necrosis) : Our data suggest that Ca ( 2+ ) inhibits caspase activation during Ca ( 2+ ) -mediated neuron death by triggering the degradation of the cytochrome c-binding protein APAF-1
Henshall et al., Cell Death Differ 2001 (Seizures) : In this study we examine the in vivo formation of the Apaf-1/cytochrome c complex and activation of caspase-9 following limbic seizures in the rat ... These data suggest seizures induce formation of the Apaf-1/cytochrome c complex prior to caspase-9 activation and caspase-9 may be a potential therapeutic target in the treatment of brain injury associated with seizures
Mori et al., Int J Oncol 2002 (Acquired Immunodeficiency Syndrome...) : In the apoptosome, cytochrome c and Apaf-1 activate caspase-9 which subsequently leads to the activation of caspase-3
Yuan et al., Am J Physiol Cell Physiol 2002 : The latter interacts with Apaf-1 to activate caspase-9 , which in turn activates downstream caspase-3
Bitzer et al., J Biol Chem 2002 : Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates
O'Reilly et al., Cell Death Differ 2002 : Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9
Brunelle et al., Apoptosis 2002 : Apoptotic signaling during oxygen deprivation occurs through the release of cytochrome c and apaf-1 mediated caspase-9 activation
Marsden et al., Nature 2002 : Because Apaf-1 requires cytochrome c to activate caspase-9 , and Bcl-2 prevents mitochondrial cytochrome c release, Bcl-2 is widely believed to inhibit apoptosis by safeguarding mitochondrial membrane integrity
Murphy et al., J Exp Med 2003 : Surprisingly, neutrophil cell-free extracts readily supported Apaf-1 dependent caspase activation, suggesting that these cells may assemble cytochrome c-independent apoptosomes ... However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1 dependent caspase activation in these cells
Zhang et al., Biochem Pharmacol 2003 (Colonic Neoplasms) : With a serial of Western blot analysis, it is revealed that gossypol induced cell cycle arrest is involved in P21 up-regulation and cyclin D1 down-regulation ; gossypol induced apoptosis triggers down-regulation of anti-apoptosis Bcl-2 members : Bcl-X ( L ), Bag-1 and Mcl-1, up-regulation of pro-apoptosis Bcl-2 member Bak, activation of caspase-3 , -6, -7, -8, and -9, up-regulation of Apaf-1 , release of cytochrome c ( cyto-c ) from mitochondria, and activation of both DFF45 and PARP
Milosevic et al., Oncogene 2003 (Adenocarcinoma...) : The release of mitochondrial apoptogenic proteins, such as cytochrome c, into the cytoplasm leading to Apaf1 dependent activation of caspase-9 is a key event in this pathway
Martin et al., Biochem Biophys Res Commun 2004 : Here we tested the ability of apo cytochrome c to inhibit caspase-9 activation induced by recombinant Apaf-1
Shimizu et al., Clin Cancer Res 2004 (Carcinoma, Hepatocellular...) : Combined treatment with low concentrations of these two agents also acted synergistically to induce apoptosis in HepG2 cells through induction of Bax and Apaf-1 , reduction of Bcl-2 and Bcl-xL, and activation of caspase-3 , -8, and -9
Zanon et al., Cancer Res 2004 (Melanoma) : Moreover, drug induced caspase-9 enzymatic activity could be not only partially but significantly reduced by caspase-2, -3, and -8 -specific inhibitors in both APAF-1 ( + ) and APAF-1 ( - ) tumor cells
Sun et al., Blood 2005 (Lymphoma, B-Cell) : Enforced expression of Apaf-1 increased its concentration in the cytosolic compartment, restored cytochrome c-dependent caspase activation, and rendered the prototypic Raji BL cell line sensitive to etoposide- and staurosporine induced apoptosis
Martin et al., J Biol Chem 2005 : Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c ... A critical component of the intrinsic apoptotic pathway is caspase-9 , which is activated by Apaf-1 in the apoptosome, a large complex assembled in response to release of cytochrome c from mitochondria ... Importantly, protein kinase A inhibits cytochrome c-dependent recruitment of procaspase-9 to Apaf-1 but not activation of caspase-9 by a constitutively activated form of Apaf-1
Riedl et al., Nature 2005 : The apoptotic protease activating factor 1 ( Apaf-1 ) controls caspase activation downstream of mitochondria
Chao et al., PLoS Biol 2005 : Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1 dependent manner
Bao et al., Cell cycle (Georgetown, Tex.) 2005 : The apoptotic protease activating factor 1, an essential protein conserved in all three species, is responsible for the activation of the initiator caspase-9 in mammalian cells
Harlan et al., Mol Psychiatry 2006 (Genetic Predisposition to Disease) : The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell
Brady et al., Mol Cell Biol 2005 : Caspase 9 is a critical component of the mitochondrial or intrinsic apoptotic pathway and is activated by Apaf-1 following release of cytochrome c from mitochondria in response to a variety of stimuli
Mantena et al., Carcinogenesis 2006 (Lung Neoplasms...) : Induction of apoptosis was associated with the release of cytochrome c, increased expression of Apaf-1 and activation of caspase 3 and poly ( ADP-ribose ) polymerase ... Dietary GSPs ( 0.2 and 0.5 %, w/w ) significantly inhibited the growth of the implanted 4T1 tumor cells and increased the ratio of Bax : Bcl-2 proteins, cytochrome c release, induction of Apaf-1 and activation of caspase 3 in the tumor microenvironment
Fettucciari et al., J Immunol 2006 (Calcium Signaling) : In GBS induced apoptosis, cytochrome c did not induce caspase-3 and -7 activation because they and APAF-1 were degraded by calpains
Cao et al., J Biol Chem 2008 : Biochemical studies reveal that the expression of c-Myc and caspase-2 is crucial for cytochrome c release from mitochondria during cytotoxic stress and that Apaf-1 is only required following cytochrome c release to activate caspases-9/-3
De Zio et al., Cell Mol Life Sci 2008 : Faf1 is expressed during neurodevelopment and is involved in Apaf1 dependent caspase-3 activation in proneural cells
Sanchez-Olea et al., J Biol Chem 2008 : Apaf-1 mediated activation of caspase-9 and caspase-3 was markedly decreased in a cytosolic fraction isolated from HeLa cells with reduced parcs expression
Zuo et al., Cell Res 2009 : Taken together, oxidative modification of caspase-9 by ROS can mediate its interaction with Apaf-1 , and can thus promote its auto-cleavage and activation
Tan et al., Cancer 2011 (Ovarian Neoplasms) : Although Apaf-1 is expressed in most ovarian cancers, the functional activity is impaired, as Apaf-1 has a diminished ability to recruit and activate caspase-9
Zhang et al., PloS one 2011 : These findings suggest that in the absence of nucleotide such as ATP, direct association of procaspase-9 with Apaf-1 leads to defective molecular timer, and thus, inhibits apoptosome mediated caspase activation
Yu et al., Environ Toxicol 2012 (Carcinoma, Squamous Cell...) : Safrole induced apoptosis was accompanied with up-regulation of the protein expression of Bax and Bid and down-regulation of the protein levels of Bcl-2 ( up-regulation of the ratio of Bax/Bcl-2 ), resulting in cytochrome c release, promoted Apaf-1 level and sequential activation of caspase-9 and caspase-3 in a time dependent manner
Gogada et al., Cell cycle (Georgetown, Tex.) 2011 : In contrast, Apaf-1 deficiency or silencing inhibited the activity of caspase-3 , pointing to a requisite role of Apaf-1 in curcumin induced apoptotic cell death ... Importantly, p21-deficiency resulted in reduced expression of Apaf-1 during curcumin treatment, indicating a requirement of p21 in Apaf-1 dependent caspase activation and apoptosis
Tzang et al., J Cell Mol Med 2012 (Lupus Erythematosus, Systemic) : Moreover, level of cytosolic cytochrome c and Apaf-1 , and activation of caspase-9 and caspase-3 were suppressed in response to cystamine treatment
Matalova et al., Arch Oral Biol 2012 : It has been shown that caspase-9 and Apaf-1 are essential for apoptosis in the PEK as well as the central caspase-3
Liu et al., PloS one 2012 : Caspase-9 inhibitor could inhibit activation of pro-caspase-3 , and the inhibition of the function of Apaf-1 with FSBA blocked apoptosis, hinting that Apaf-1 could be involved in Sl-1 cell apoptosis induced by AfMNPV
Hu et al., Proc Natl Acad Sci U S A 1998 : Bcl-XL interacts with Apaf-1 and inhibits Apaf-1 dependent caspase-9 activation
Slee et al., J Cell Biol 1999 : In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1 mediated activation of caspase-9