A NOVEL HUMAN PROTEASE SIMILAR TO THE INTERLEUKIN-1-BETA CONVERTING-ENZYME INDUCES APOPTOSIS IN TRANSFECTED CELLS

We have identified a novel cDNA encoding a protein (named TX) with >50 % overall sequence identity with the interleukin-1 beta converting enz yme (ICE) and similar to 30 % sequence identity with the ICE homologs NEDD-2/ ICH-1(L) and CED-3. A computer homology model of TX was constr ucted based on the X-ray coordinates of the ICE crystal recently publi shed. This model suggests that TX is a cysteine protease, with the P1 aspartic acid substrate specificity retained. Transfection experiments demonstrate that TX is a protease which is able to cleave itself and the p30 ICE precursor, but not to generate mature IL-1 beta from pro-I L-1 beta. In addition, this protein induces apoptosis in transfected C OS cells. TX therefore delineates a new member of the growing Ice/ced- 3 gene family coding for proteases with cytokine processing activity o r involved in programmed cell death.