Role of caspases in apoptosis and disease.

ABSTRACT

Apoptosis, a genetically governed process of eliminating cells in response to a variety of stimuli provides protection against cancer and viral infections as well as maintains homeostasis. Recent studies using both molecular and cloning approaches, and in vitro systems have identified a class of highly specific proteases, termed caspases, that appear to have an important role in apoptotic execution. Caspases are synthesized as precursor molecules that require processing at specific aspartate residues to produce the active enzyme which in turn leads to the cleavage of various death substrates that lead to morphological changes typical of apoptosis. This review discusses caspases, their inhibitors and regulators. Since cytotoxic drugs used in chemotherapy of leukemia's and solid tumors cause apoptosis in target cells, elucidating the consequences of proteolytic activity occupies a central role for understanding of the molecular mechanism of apoptosis which can help us to use the caspase inhibitors as targets of therapy.