The cloning and identification of two novel isoforms of human ICE

Human interleukin-l converting enzyme (ICE) is a cytoplasmic cysteine protease that processes the 31 KDa inactive precursor of interleukin-1 into the 17 KDa active pro-inflammatory cytokine IL-I. To understand the mechanism of ICE-activation in apoptosis, we established in vitro long-term T cell culture from freshly isolated PBMCs of lupus patients or normal family members. We analyzed the expression of ICE mRNA by the RT-PCR technique. This resulted in the identification and cloning of two new alternatively spliced ICE mRNA isoforms and were designated as ICE-2a and ICE-2b. The 5' end of ICE-2a and ICE-2b (from coding sequence bp 1 to 274) are 100% homologous to ICE-a and ICE-. The 3' end of ICE-2a and ICE-2b are identical, but only have 85% homologous to human ICE exon 4. In ICE-2a, there were 62 bp sequence (bp 275 to 337) which is deleted in ICE-2b, is not homologous to any known ICE sequence, instead they are 68% homologous to ZYMV polyprotein (pi protease). Interestingly, the ICE-2a and ICE-2b are highly expressed in the freshly isolated PBMC, but disappeared after stimulation with PHA/IL-2. These observations suggested that ICE-2a and ICE-2b may play an important role in the regulation of programmed cell death in humans.