Structure and chromosome localization of the human CASP8 gene

The human CASP8 gene, whose product is also known as caspase 8 and FLICE, e ncodes an interleukin-1 beta converting enzyme (ICE)-related cysteine prote ase that is activated by the engagement of several different death receptor s. Caspase 8 is immediately recruited to the Fas receptor once it oligomeri zes, and its protease activity is crucial for the apoptotic response genera ted by the resulting death-inducing signaling complex (DISC). We report her e that the CASP8 gene contains at least 11 exons spanning similar to 30 kb on human chromosome band 2q33-34. This region of human chromosome 2 was pre viously reported as the location of the CASP10 gene, whose product is close ly related to caspase 8. Chromosome 2 band q33-34 is also involved in tumor igenesis, with loss of heterogeneity (LOH) being reported in a number of tu mors. We also report EcoRI and HindIII polymorphisms that may prove to be u seful in disease analysis. Both caspases 8 and 10 contain long pro-domains with duplicated death effector domains (DEDs), as well as their correspondi ng cysteine protease catalytic domains. Thus, it appears that CASP8 and CAS P10 have evolved by tandem gene duplication, much like the CASP1, CASP4 and CASP5 gene cluster on human chromosome 11q22.2-22.3. (C) 1999 Elsevier Sci ence B.V. All rights reserved.