M. Miura et al., TUMOR NECROSIS FACTOR-INDUCED APOPTOSIS IS MEDIATED BY A CRMA-SENSITIVE CELL-DEATH PATHWAY, Proceedings of the National Academy of Sciences of the United Statesof America, 92(18), 1995, pp. 8318-8322
We report here that the activation of the interleukin 1 beta (IL-1 bet
a)-converting enzyme (ICE) family is likely to be one of the crucial e
vents of tumor necrosis factor (TNF) cytotoxicity, The cowpox virus Cr
mA 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, anot
her member of the Ice/ced-3 family of genes, We found that the CrmA-ex
pressing HeLa cells are resistant to TNF-alpha/cycloheximide (CHX)-ind
uced apoptosis, Induction of apoptosis in HeLa cells by TNF-alpha/CHX
is associated with secretion of mature IL-1 beta, suggesting that an I
L-1 beta-processing enzyme, most likely ICE itself, is activated by TN
F-alpha/CHX stimulation. These results suggest that one or more member
s of the ICE family sensitive to CrmA inhibition are activated and pla
y a critical role in apoptosis induced by TNF.