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Apoptotic protease activating factor-1 (Apaf-1)

Apoptosis is a form of programmed cell death in multicellular organisms. Its dysfunction plays a crucial role in different human diseases, such as cancer and neurological degenerative disorders. In the process of apoptosis, a complex known as the apoptosome is formed from apoptotic protease activating factor-1 (Apaf-1), procaspase-9, and cytochrome c/dATP. The apoptosome comprises seven molecules of Apaf-1 arranged in a symmetric, wheel-shaped structure. Apaf-1 contains an N-terminal caspase recruitment domain (CARD), which is responsible for recruiting caspase-9, a nucleotidebinding oligomerization domain (NOD), and 13 WD40 repeats, which are thought to interact with cytochrome c. Oligomerization of Apaf-1 leads to autoactivation of procaspase-9 that in turn cleaves caspase-3, ultimately causing cell death. The structure of the apoptosome thus constitutes a cellular “death wheel” In many cell types, the apoptosome is dispensable for stress-induced apoptosis and it serves to amplify rather than initiate the caspase cascade and must be more important in certain cell types.

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