THE STRUCTURE AND COMPLETE NUCLEOTIDE-SEQUENCE OF THE MURINE GENE ENCODING INTERLEUKIN-1-BETA CONVERTING-ENZYME (ICE)

Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the p recursor of the cytokine IL-1 beta to a mature, biologically active fo rm in monocytes and macrophages. To further understand the role of ICE in regulating IL-1 beta-mediated biological functions, we have isolat ed several genomic clones encoding the full-length murine ICE gene. So uthern blot comparison of murine genomic DNA and the clones indicates that ICE is a compact, single-copy gene 8616 bp in size. We sequenced the entire gene as well as a 1.0-kb segment upstream of the coding reg ion and determined that the gene consists of 10 exons whose organizati on parallels the functional organization of the ICE proenzyme in that the prodomain and p20 and pin subunits of ICE are encoded by three clu sters of exons. Two initiation sites, 37 and 32 nucleotides upstream o f the initiator methionine, were identified by primer extension analys is. The 5' region of the ICE gene lacks a TATA box, a CAAT box, and SP 1 sites. However, the presence of a completely conserved 14-bp sequenc e spanning the transcription initiation site of both the murine and th e human ICE genes suggests that this sequence plays a role in transcri ption. (C) 1994 Academic Press, Inc.