Figure 3.

Intrinsic proapoptotic signaling. Death signals and survival signals affect the control level of cellular kinases in opposite directions (prosurvival and proapoptotic). Kinases may affect p53, proapoptotic BH3-only proteins, antiapoptotic Bcl-2 proteins (Bcl-2, Bcl-x_L, A1, Mcl-1, Bcl-w), proapoptotic, multidomain Bcl-2 proteins (Bax and Bak) as well as mitochondrial functions. The BH3-only protein Bid is cleaved by caspase-8 in response to death ligands, resulting in activated, truncated Bid (tBid). The activation of Bcl-2 proteins results in the release of proapoptotic, mitochondrial factors such as cytochrome c (CytC), second mitochondria-derived activator of caspase (Smac), apoptosis-inducing factor (AIF), and endonuclease G (EndoG). In contrast, reactive oxygen species (ROS) production may result from mitochondrial dysfunction but appears as largely independent of Bcl-2 proteins. Further abbreviations: Csp-3, -6, -7, -9, caspases; cIAPs, cellular inhibitor of apoptosis proteins; Apaf-1, apoptotic protease activating factor; ATP, adenosine triphosphate. Arrowheads indicate activation while blunt ends indicate inhibition; scissors () indicate protease activity. Proapoptotic factors and mechanisms are shown in red and orange, while antiapoptotic factors and mechanisms are shown in green. Further explanations are given in the text.