Apoptosis and Cell Cycle

Programmed Cell Death
Programmed cell death (PCD), or apoptosis, can be triggered by a wide range of stimuli, including cell surface receptors like Fas or tumor necrosis factor receptor 1 (TNFR1). It constitutes a system for the removal of unnecessary, aged, or damaged cells that are regulated by the interplay of proapoptotic and antiapoptotic proteins of the Bcl-2 family. The proapoptotic proteins Bax, Bad, Bid, Bik, and Bim contain an a-helical BH3 death domain that fits the hydrophobic BH3 binding pocket on the antiapoptotic proteins Bcl-2 and Bcl-xL, forming heterodimers that block the survival-promoting activity of Bcl-2 and Bcl-xL. Thus, the relative abundance of proapoptotic and antiapoptotic proteins determines the susceptibility of the cell to programmed death. The proapoptotic proteins act at the surface of the mitochondrial membrane to decrease the mitochondrial transmembrane potential and promote leakage of cytochrome c. In the presence of dATP, cytochrome c complexes with and activates Apaf-1. Activated Apaf-1 binds to downstream caspases, such as pro-caspase-9, and processes them into proteolytically active forms. This begins a caspase cascade resulting in apoptosis. Smac/Diablo is released from the mitochondria and blocks IAP proteins that normally interact with caspase-9 to inhibit apoptosis. The graphic shows the conserved apoptotic pathway in C. elegans. CED-3 encodes a caspase whose function is facilitated by CED-4, which is highly similar to Apaf-1. CED-4 function is blocked by CED-9, which protects cells against apoptosis and is similar to the human antiapoptotic protein Bcl-2. CED-9 activity is inhibited by EGL-1, which is similar to the proapoptotic Bcl-2 family members.
An Overview of Programmed Cell Death