text: Apoptosis, the process of programmed cell death, involves complex signaling pathways and cascades of molecular events. This process is needed for proper development during embryonic and fetal growth where there is destruction and reconstruction of cellular structures. In adult organisms, apoptosis is needed to maintain differentiated tissue by striking the balance between proliferation and cell death. It is known that intracellular proteases called caspases degrade the cellular contents of the cell by proteolysis upon activation of the death pathway.
  Mammalian cells have two main pathways that lead to apoptosis.
  1. Extrinsic pathway: Initiated by extrinsic ligands binding to death receptors on the surface of the cell. An example of this is the binding of tumour necrosis factor-alpha (TNF-alpha) to TNF-alpha receptor. An example of a TNF receptor is Fas (CD95), which recruits activator caspases like caspase-8 upon binding TNF at the cell surface. The activation of the initiator caspases then initiates a downstream cascade of events that results in the induction of effector caspases that function in apoptosis.
  2. Intrinsic pathway: This pathway is initiated by intracellular or environmental stimuli. It is focused on detecting the improper functioning of the mitochondria in the cell and, as a result, activates signaling pathways to commit suicide. The membrane permeability of the mitochondria increases and particular proteins are released into the cytoplasm that facilitates the activation of initiator caspases. The particular protein released from the mitochondria is cytochrome c. Cytochrome c then binds to Apaf-1 in the cytosol and results in the activation of initiator caspase-9. The activation of the initiator caspases then initiates a downstream cascade of events that results in the induction of effector caspases that function in apoptosis.
  One family of proteins called IAPs plays a role in regulating cell death by inhibiting the process. IAPs like survivin, inhibit apoptosis by physically binding to and inhibiting proper caspase function. The function of IAPs is evolutionarily conserved as Drosophila homologues of IAPs have been shown to be essential for cell survival.
  IAPs have been implicated in studies to have a regulatory effect on cell division. Yeast cells with knock-outs of certain IAP genes did not show problems associated with cell death, but showed defects in mitosis characterized by improper chromosome segregation or failed cytokinesis.
  Deletion of particular IAPs does not seem to have a profound effect on the cell-death pathway as there is a redundancy of function by the many IAPs that exist in a cell. They have been implicated, however, to play a role in maintaining an anti-apoptotic environment intracellularly. Changing the expression of particular IAPs has shown an increase in spontaneous cell death induction or increased sensitivity to death stimuli.