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. 1995 Aug 29;92(18):8318-22.
doi: 10.1073/pnas.92.18.8318.

Tumor Necrosis Factor-Induced Apoptosis Is Mediated by a CrmA-sensitive Cell Death Pathway

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Free PMC article

Tumor Necrosis Factor-Induced Apoptosis Is Mediated by a CrmA-sensitive Cell Death Pathway

M Miura et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

We report here that the activation of the interleukin 1 beta (IL-1 beta)-converting enzyme (ICE) family is likely to be one of the crucial events of tumor necrosis factor (TNF) cytotoxicity. The cowpox virus CrmA protein, a member of the serpin superfamily, inhibits the enzymatic activity of ICE and ICE-mediated apoptosis. HeLa cells overexpressing crmA are resistant to apoptosis induced by Ice but not by Ich-1, another member of the Ice/ced-3 family of genes. We found that the CrmA-expressing HeLa cells are resistant to TNF-alpha/cycloheximide (CHX)-induced apoptosis. Induction of apoptosis in HeLa cells by TNF-alpha/CHX is associated with secretion of mature IL-1 beta, suggesting that an IL-1 beta-processing enzyme, most likely ICE itself, is activated by TNF-alpha/CHX stimulation. These results suggest that one or more members of the ICE family sensitive to CrmA inhibition are activated and play a critical role in apoptosis induced by TNF.

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