CGC Bibliography Paper 3104

Proteases to die for.

Cryns V, Yuan J

Medline:

98283905

Citation:

Genes & Development 12: 1551-1570 1998

Type:

REVIEW

Genes:

ced-3 ced-4 ced-9

Abstract:

Apoptosis or programmed cell death (PCD) is a genetically regulated, cellular suicide mechanism that plays a crucial role in development and in the defense of homeostasis. Cells respond to a variety of disparate signals by committing suicide through a series of dramatic but remarkably uniform events. Morphologically, cells undergoing apoptosis demonstrate nuclear/cytoplasmic condensation and membrane protrusions. These initial changes are followed by fragmentation of the nuclear contents and subsequent encapsulation of these fragments into "apoptotic bodies" that are quickly and unobtrusively consumed by adjacent cells, thereby leaving little trace of the apoptotic cell's prior existence. Biochemically, apoptotic cells are characterized by reduction in the mitochondrial transmembrane potential, intracellular acidification, production of reactive oxygen species, externalization of phosphatidylserine residues in membrane bilayers, selective proteolysis of a subset of cellular proteins, and degradation of DNA into internucleosomal fragments. These characteristic manifestations of apoptosis reflect the activation of an intrinsic cell death apparatus that has been exquisitely conserved during evolution. At the core of this death apparatus is a novel family of proteases related to the Caenorhabditis elegans cell death gene product CED-3, the so-called caspases (cysteine proteases with aspartate-specificity), that are universal effectors of apoptotic cell death. Although several features of these pro-apoptotic proteases have been summarized previously, the present review will focus on recent insights into (1) the regulation of caspases (both positively and negatively) by other components of the cell death apparatus; and (2) the mechanisms by which caspase activation leads to the demise of the cell.