cAPAF1

cAPAF1 is a protein related to the apoptosis protease activating factor 1 (APAF1) and is discussed in the literature as a cytosolic or variant form of APAF1. In many contexts, cAPAF1 is described as participating in the intrinsic (mitochondrial) pathway of apoptosis, where it contributes to the formation of the apoptosome and the activation of initiator caspases.

Structurally, APAF1 family proteins typically contain an N-terminal caspase recruitment domain (CARD), a central NOD-like nucleotide-binding and oligomerization (NB-ARC) domain, and C-terminal WD40 repeats. Upon release of cytochrome c from mitochondria and binding of ATP or dATP, these proteins undergo conformational changes that promote oligomerization into a heptameric apoptosome. The apoptosome then recruits procaspase-9 through CARD–CARD interactions, leading to autocatalytic activation of caspase-9 and the downstream caspase cascade that drives apoptosis.

Regulation of cAPAF1/apaf-1 and the apoptosome involves multiple layers, including inhibition by IAPs such as XIAP, post-translational modifications, and interactions with BCL-2 family proteins that influence mitochondrial outer membrane permeabilization. Inhibitory proteins and competing signaling pathways can modulate the sensitivity of cells to apoptotic stimuli.

Biological and clinical relevance centers on the role of APAF1-related pathways in cell fate decisions. Proper APAF1/cAPAF1 function is essential for efficient mitochondrial apoptosis, whereas loss or dysregulation can contribute to cancer cell survival, therapy resistance, or neurodegenerative disease processes. In some studies, cAPAF1 is used to denote a cytosolic or isoform-specific variant, and exact identity may vary by species, tissue, or experimental context.