IDENTIFICATION OF 5 NEW GENES, CLOSELY-RELATED TO THE INTERLEUKIN-1-BETA CONVERTING-ENZYME GENE, THAT DO NOT ENCODE FUNCTIONAL PROTEASES

Interleukine-1 beta converting enzyme (ICE) was the first identified m ember of a growing family of cysteine proteases that now includes ten mammalian homologs. Within this large family, two functional proteins, denoted TX and TY share 60% amino-acid identity with ICE in the matur e protein and, together with ICE, constitute the ICE subfamily. The pr esent study describes the identification of five new gene sequences, d enoted S1-S5, closely related to ICE and TX and belonging to this subf amily. Sequences were identified using genomic Southern-blot analysis of human DNA with probes corresponding to ICE and TX exon 6. Using PCR amplification and cloning, the complete exon-6 sequence of these new genes was identified; three exhibit around 90% identity with Ice withi n exon 6, whereas the two others share about 70% identity with Ice. Ex amination of open reading frames and of amino acids essential for ICE activity indicate that none of these genes encodes for a functional pr otease. In conclusion, extensive analysis of the genes closely related to Ice shows that the Ice subfamily is constituted of eight members. Three of them encode for functional proteases (ICE, TX and TY) whereas the remaining members probably correspond to pseudogenes.