Apoptotic Peptidase Activating Factor 1 (APAF1)

CED4; Apoptotic Protease Activating Factor

SPN	V758
HGNC	576
MGI	1306796
PubMed	15105372
RGD	620575
UniProt	O14727
Wiki	Apaf-1

Apoptotic peptidase activating factor 1 is a proteincontains several copies of the WD40 repeat domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, 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. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.Alternative splicing results in several transcript variants encoding different isoforms.

Reference

"Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3."
Cell 90:405-413(1997) [PubMed] [Europe PMC] [Abstract]

"Three new types of Apaf-1 in mammalian cells."
Biochem. Biophys. Res. Commun. 261:746-749(1999) [PubMed] [Europe PMC] [Abstract]

"Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation."
J. Biol. Chem. 274:17941-17945(1999) [PubMed] [Europe PMC] [Abstract]

"Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis."
EMBO J. 18:3586-3595(1999) [PubMed] [Europe PMC] [Abstract]

"APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line."
Biochem. Biophys. Res. Commun. 306:537-543(2003) [PubMed] [Europe PMC] [Abstract]

"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]

"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization."
Mol. Cell 1:949-957(1998) [PubMed] [Europe PMC] [Abstract]

"Apaf-1 is a transcriptional target for E2F and p53."
Nat. Cell Biol. 3:552-558(2001) [PubMed] [Europe PMC] [Abstract]

"Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein."
J. Biol. Chem. 279:39942-39950(2004) [PubMed] [Europe PMC] [Abstract]

"Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1."
Mol. Cell 25:181-192(2007) [PubMed] [Europe PMC] [Abstract]

"Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP."
Biochem. Biophys. Res. Commun. 407:158-162(2011) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling."
J. Mol. Biol. 293:439-447(1999) [PubMed] [Europe PMC] [Abstract]

"Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1."
Cell Death Differ. 6:1125-1132(1999) [PubMed] [Europe PMC] [Abstract]