Figure 2. Survivin (SVN) pathways to apoptosis . Activation of cell death pathways can be initiated through different mechanisms, including through ligand binding (FasL,TNF) to a death receptor on the cell surface (extrinsic pathway) or via direct mitochondrial signaling (intrinsic pathway). The mitochondrial pathway is initiated by activation of the Bax/Bcl-2 pathway leading to the release of apoptotic factors such as cytochrome c (cyt c) and apoptosis-inducing factor (AIF) from the mitochondrial intermembrane space into the cytoplasm. The release of cytochrome c from mitochondria results in caspase-3 activation through formation of the cytochrome c/Apaf-1(apoptotic peptidase activating factor-1)/caspase-9 apoptosome complex. Caspase-3 cleaves a number of substrates including cytoskeletal proteins and DNA. Caspase-activated DNase (CAD) and inhibitor of CAD(ICAD) initiate cleavage and fragmentation of DNA. The inhibitors of apoptosis (IAPs) inhibit cell death by physically interacting with caspases. Survivin has been shown to inhibit apoptosis through caspase-dependent and independent pathways.