Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.^[1][2][3] APAF-1 and CED-4 homologs have been found in all currently sequenced animal genomes.

Function

This gene encodes a cytoplasmic protein that forms one 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 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.^[4] Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.

Alternative splicing results in several transcript variants encoding different isoforms.^[1]

Structure

The first crystal structure of the first two (CARD and NB-ARC) domains of the Apaf-1 protein was solved in the laboratory of Yigong Shi.^[5] It 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.

Discovery

The Apaf-1 protein was identified by Xiaodong Wang.^[2]

Interactions

APAF1 has been shown to interact with NLRP1,^[6] Caspase-9,^{[6][7][8][9][10]} APIP,^[7] BCL2-like 1^[9][10] and HSPA4.^[11]

References

Further reading

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