Abstract
Interleukin-2 (IL-2)-dependent T cell clone CTLL-2 underwent apoptosis by deprivation of IL-2 from culture medium. The decrease in the anti-apoptotic Bcl-XL protein level was observed during apoptosis after IL-2 withdrawal. We found that Bcl-XL protein was cleaved to produce two 18 kDa fragments during CTLL-2 cell apoptosis. When the activation of caspases was suppressed by overexpressing human Bcl-2 protein or by the addition of caspase inhibitors, cleavage of Bcl-XL protein was suppressed in vivo. Bcl-XL protein cleavage by incubation with apoptosed CTLL-2 cell lysate was suppressed by the caspase-3/CPP32-specific tetrapeptide inhibitor in vitro. Therefore, caspase-3/CPP32-like proteases were activated and involved in the cleavage of Bcl-XL protein during CTLL-2 cell apoptosis. We found that Bcl-XL protein was cleaved by caspase-3/CPP32 at two sites in the loop domain (i.e., HLAD61↓S and SSLD76↓A). The transfection of the carboxy-terminal 18 kDa Bcl-XL fragment increased the sensitivity to apoptosis. These results indicate that caspase-3/CPP32-like proteases cleaved anti-apoptotic Bcl-XL protein and resulted in accelerated apoptotic cell death.
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Fujita, N., Nagahashi, A., Nagashima, K. et al. Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases. Oncogene 17, 1295–1304 (1998). https://doi.org/10.1038/sj.onc.1202065
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DOI: https://doi.org/10.1038/sj.onc.1202065
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