FUNCTIONAL-CHARACTERIZATION OF THE PRODOMAIN OF INTERLEUKIN-1-BETA-CONVERTING ENZYME

Interleukin 1 beta-converting enzyme (ICE) has been identified as the main protease responsible for maturation of the prodomain of interleuk in-1 beta. Recently, it was shown to belong to a larger gene family, m embers of which play an important role in programmed cell death. A com mon feature of the ICE family proteases is the presence of a prodomain that has been hypothesized to keep the enzyme in an inactive form. Ex pression analysis in yeast revealed autocatalytic degradation of p45IC E, but not of p30ICE lacking a prodomain. We further demonstrate that p45ICE, in which the critical cysteine has been mutated, is still able to dimerize in vivo, Dimerization requires the prodomain and occurs p rior to autoprocessing. These results provide evidence for a regulator y role of the prodomain of ICE.