ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein ced-3 is activated during fas- and tumor necrosis factor-induced apoptosis

Members of the ICE/ced-3 gene family have been implicated as components of the cell death pathway. Based on similarities with the structural prototype interleukin-1 beta-converting enzyme (ICE), family members are synthesized as proenzymes that are proteolytically processed to form active heterodimeric enzymes. In this report, we describe a novel member of this growing gene family, ICE-LAPS, which is closely related to the death effector Yama/CPP32/Apopain. Pro-ICE-LAPS is a 35-kDa protein localized to the cytoplasm and expressed in a variety of tissues and cell lines. Overexpression of a truncated version of ICE-LAPS (missing the pro-domain) induces apoptosis in MCF7 breast carcinoma cells. Importantly, upon receipt of a death stimulus, endogenous ICE-LAPS is processed to its subunit forms, suggesting a physiological role in cell death. This is the first report to demonstrate processing of a native ICE/ ced-3 family member during execution of the death program and the first description of the subcellular localization of an ICE/ced-3 family member.