Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[5][6][7]
Function
The protein was identified in the laboratory of
Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC and dATP.[8] This gene encodes a cytoplasmic protein that forms one of the central hubs in the
apoptosis regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (
CARD), an
ATPase domain (NB-ARC), few short helical domains and then several copies of the
WD40 repeat domain. Upon binding
cytochrome c and
dATP, this protein forms an oligomeric
apoptosome. The apoptosome binds and cleaves
Procaspase-9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by
Guy Salvesen suggests that the apoptosome may induce
caspase-9 dimerization and subsequent
autocatalysis.[9] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
APAF1 contains a
CARD domain with a
Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[10]
^Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 87 (3–4): 252–3.
doi:
10.1159/000015436.
PMID10702682.
S2CID10377371.
Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y (Jun 1999). "Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1". Nature. 399 (6736): 549–57.
Bibcode:
1999Natur.399..549Q.
doi:
10.1038/21124.
PMID10376594.
S2CID4403525.
Drosopoulos NE, Walsh FS, Doherty P (Jun 1999). "A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade". Molecular and Cellular Neurosciences. 13 (6): 441–9.
doi:
10.1006/mcne.1999.0758.
PMID10383829.
S2CID35458154.
Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[5][6][7]
Function
The protein was identified in the laboratory of
Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC and dATP.[8] This gene encodes a cytoplasmic protein that forms one of the central hubs in the
apoptosis regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (
CARD), an
ATPase domain (NB-ARC), few short helical domains and then several copies of the
WD40 repeat domain. Upon binding
cytochrome c and
dATP, this protein forms an oligomeric
apoptosome. The apoptosome binds and cleaves
Procaspase-9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by
Guy Salvesen suggests that the apoptosome may induce
caspase-9 dimerization and subsequent
autocatalysis.[9] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
APAF1 contains a
CARD domain with a
Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[10]
^Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 87 (3–4): 252–3.
doi:
10.1159/000015436.
PMID10702682.
S2CID10377371.
Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y (Jun 1999). "Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1". Nature. 399 (6736): 549–57.
Bibcode:
1999Natur.399..549Q.
doi:
10.1038/21124.
PMID10376594.
S2CID4403525.
Drosopoulos NE, Walsh FS, Doherty P (Jun 1999). "A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade". Molecular and Cellular Neurosciences. 13 (6): 441–9.
doi:
10.1006/mcne.1999.0758.
PMID10383829.
S2CID35458154.