FIGURE 2.

The programmed cell death- via intrinsic and extrinsic pathways in normal mammalian cells. Intrinsic and extrinsic pathways result in the activation of a family of protease enzymes called Caspase proteins. The intrinsic pathway is promoted by cellular stresses that modulate Bcl-2 family proteins and activates Bak and Bax. In the indirect activation, upregulation of BH3-only proteins will act as inhibitors of anti-apoptotic proteins by competing for their binding with Bax and Bak proteins, leading Bax and Bak to oligomerize. In the direct activation, upregulation of BH3 activators proteins directly activates Bax and Bak. This activation leads to mitochondrial outer membrane permeabilization (MOMP), subsequently Cytochrome C and SMAC proteins release into the cytosol, causing the downstream of Caspase activation that ends with apoptosis. The extrinsic pathway is promoted by death receptors activation. This leads to activation of initiator Caspases 8 and 10, which can regulate the downstream executioner Caspase such as Caspase 3 and 7 to drive full commitment to apoptosis. Moreover, Caspases 8 and 10 can activate Bid, which in turn activates Bak and Bax to induce MOMP which establishes the link between the extrinsic and intrinsic pathways.