IDENTIFICATION OF A NEW CASPASE HOMOLOG - CASPASE-14

Caspases are cysteinyl aspartate-specific proteinases, many of which p lay a central role in apoptosis, Here, we report the identification of a new murine caspase homologue, viz, caspase-14, It is most related t o human/murine caspase-2 and human caspase-9, possesses all the typica l amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain, Murine caspase-14 shows 83% similarity to human caspase-14, Human caspase-14 is assigned to chromosome 19p13.1. Northern blot analysis revealed th at mRNA expression of caspase-14 is undetectable in all mouse adult ti ssues examined except for skin, while it is abundantly expressed in mo use embryos. In contrast to many other caspase family members, murine caspase-14 is not cleaved by granzyme B, caspase-1, caspase-2, caspase -3, caspase-6, caspase-7 or caspase-11, but is weakly processed into p 18 and p11 subunits by murine caspase-8, No aspartase activity of muri ne caspase-14 could be generated by bacterial or yeast expression. Tra nsient overexpression of murine caspase-14 in mammalian cells did not elicit cell death and did not interfere with caspase-8-induced apoptos is. In conclusion, caspase-14 is a member of the caspase family but no proteolytic or biological activities have been identified so far. The high constitutive expression levels in embryos and specific expressio n in adult skin suggest a role in ontogenesis and skin physiology.