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Apoptosis or Programed Cell Death is the process by which cells
commit suicide. The program to apotose is present in all nucleated
cells of multicellular organisms and probably the default state of a
cell.In other words, if a cell does not receive a survival or growth
signal it will go on and die. Apoptosis plays an important role in
tissue homeostasis and a reduction in the rate of apotosis has been
shown to contribute to tumor formation. It has also been suggested
that a loss of the propensity to apoptose may contribute to
drug resistance in cancer.
A model for tissue homeostasis
In recent years many mechanistic steps during apoptosis have been elucidated at the molecular level. It is now well accepted that the process of apoptosis is mediated through the activation of a proteolytic cascade made of caspases (formarly known as ICE-proteases) that eventually leads to the hallmarks of apoptosis such as DNA laddering and chromatin condensation.In contrast, much less is known about the regulation of apoptosis. While it is thought that the bcl-2 family of proteins plays a pivotal role in the of apoptosis, their biochmeical function remains obscure. Recent evidence suggests that mitochondrial membrane depolarization and permeability transition may be an early and possibly the first irreversible step in the induction of apoptosis, and that bcl-2 inhibits this step. However, little is known how apoptosis-inducing agents lead to mitochondrial membrane depolarization, and it is not known whether this isan obligatory step for all apoptosis inducers. Thus, two main questions in apoptosis are 1) what is the biochemical function of bcl-2 and 2) what role, if any, do mitochondria play during apoptosis. Since bcl-2 is located in the mitochondrial outer membrane, these two questions are probably linked. Current research in the SCB program and at the Wadsworth Center concentrate on those questions.
A possible model for the regulation of apoptosis
Last edited 4/11/97scbwebmaster
