Caspases: their intracellular localization and translocation during apoptosis

The activation of the caspase family of proteases has been detected in nume rous cell systems and appears to function as a common pathway through which apoptotic mechanisms may operate. Caspases are synthesized as precursors ( pro-caspases) and are converted into mature enzymes by apoptotic signals. T he effects of caspases in apoptosis are accomplished by the cleavage of num erous proteins located in different intracellular compartments. In the pres ent study we have addressed the question of the subcellular localization of different pro- and active caspases as well as several other proteins, such as Apaf-1, calpain and DFF, which also play important roles in the apoptot ic process. We found that at least three pro-caspases (pro-caspases-2, -3 a nd -9) were present in both the mitochondrial and cytosolic fractions of un treated Jurkat T lymphocytes, Only pro-caspase-2 was found in the nuclear f raction. Pro-caspases-7 and -8 were found only in the cytosolic fraction. I n apoptotic cells, caspases-3, -8 and -9 were present in the cytosolic frac tion, whereas caspases-3 and -9 were also found in the mitochondrial fracti on and caspase-7 in the microsomal fraction. Caspases-2 and -3 were present in the nuclear fraction. The selective localization of pro-caspases in dif ferent subcellular compartments may play an important, but yet unknown, rol e in their activation. The translocation of active caspases to other subcel lular compartments appears to be critical for the development of the apopto tic process.