Caspases: their intracellular localization and translocation during apoptosis.
The activation of the caspase family of proteases has been detected in numerous 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. The effects of caspases in apoptosis are accomplished by the cleavage of numerous proteins located in different intracellular compartments. In the present 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 apoptotic process. We found that at least three pro-caspases (pro-caspases-2, -3 and -9) were present in both the mitochondrial and cytosolic fractions of untreated Jurkat T lymphocytes. Only pro-caspase-2 was found in the nuclear fraction. Pro-caspases-7 and -8 were found only in the cytosolic fraction. In apoptotic cells, caspases-3, -8 and -9 were present in the cytosolic fraction, whereas caspases-3 and -9 were also found in the mitochondrial fraction and caspase-7 in the microsomal fraction. Caspases-2 and -3 were present in the nuclear fraction. The selective localization of pro-caspases in different subcellular compartments may play an important, but yet unknown, role in their activation. The translocation of active caspases to other subcellular compartments appears to be critical for the development of the apoptotic process.
Zhivotovsky
B
B
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden.
Samali
A
A
Gahm
A
A
Orrenius
S
S
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D001693:Biological Transport, Active; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D011506:Proteins / Q000378:metabolism
C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D004792:Enzyme Precursors; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D002154:Calpain; D020169:Caspases