CHARACTERIZATION OF 7 MURINE CASPASE FAMILY MEMBERS

Seven members of the murine caspase (mCASP) family mere cloned and fun ctionally characterized by transient overexpression: mCASP-1 (mICE), m CASP-2 (Ich1), mCASP-3 (CPP32), mCASP-6 (Mch2), mCASP-7 (Mch3), mCASP- 11 (TX) and mCASP-12. mCASP-11 is presumably the murine homolog of hum an CASP-4. Although mCASP-12 is related to human CASP-5 (ICE(rel)-III) , it is most probably a new CASP-1 family member. On the basis of sequ ence homology, the caspases can be divided into three subfamilies: fir st, mCASP-1, mCASP-11 and mCASP-12; second, mCASP-2; third, mCASP-3, m CASP-6 and mCASP-7. The tissue distribution of the CASP-1 subfamily tr anscripts is more restricted than that of the CASP-3 subfamily transcr ipts, suggesting that the transcriptional regulation of the CASP membe rs within one subfamily is related, but is quite different between the CASP-1 and the CASP-3 subfamilies. Transient overexpression of each o f the seven CASPs induced apoptosis in mammalian cells. Only two, mCAS P-1 as well as mCASP-3, mere able to process precursor interleukin (IL )-1 beta to biologically active IL-1 beta. In addition, mCASP-3 is the predominant PARP-cleaving enzyme in vivo. (C) 1997 Federation of Euro pean Biochemical Societies.