APAF1

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APAF1

A gene on chromosome 12q23.1 that encodes a cytoplasmic protein, which initiates apoptosis. Apoptotic peptidase-activating factor 1 contains several copies of the WD-40 domain, a caspase recruitment domain (CARD) and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, APAF-1 forms an oligomeric apoptosome, which binds and cleaves caspase-9 preproprotein, releasing the activated form, which stimulates the caspase cascade that commits the cell to apoptosis.
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Como ejemplo de esto estan los estudios en Chile, de los genes APAF1, ASSP1, p73 y FHIT,p15, p16, ESR1, IGSF4, SOCS1(9); en Colombia, de los genes RARB y DAPK;CDKN2B y DBC1(10);en Brasil, del gen CDKN2B (p15) (11) y en Espana de CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, Apaf-1, DAPK, Parkin, LATS-1(12).
Literaturde CDH-1, RASSF1A gibi genlerdeki hipermetilasyonun yuksek tumor sinifi ile APAF-1, IGFBP3, [p16.
When cytochrome c accumulates in the cytosol, it complexes with procaspase-9 and Apaf-1 to form the "apoptosome", which in turn activates caspase-3 (Figure 2) [6].
One major pathway in cellular death is apoptosis that involves the release of cytochrome C from mitochondria that in turn binds to a protein known as Apaf-1 (apoptotic protease activating factor 1) and triggers its oligomerisation and subsequent execution of programmed cell death [2].
Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.
Cytochrome c recruits Apaf-1 and pro-caspase-9 to compose the apoptosome, which triggers a caspase 9/3 signaling cascade, culminating in apoptosis.
It is thought that BCL-2 has an additional ability to prevent caspase activation by sequestrating Apaf-1 (Hu et al.
Cyt C cannot therefore combine with Apaf-1 in the cytosol to activate caspase-9, which in turn cannot activate caspase-3 and caspase-7 to initiate the apoptotic cascade (Walter et al.