◀ Back to CASP4
APAF1 — CASP4
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
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
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