Structure and function of interleukin-1β converting enzyme

Publisher Summary This chapter describes the structure and function of interleukin-1β (IL-1β) converting enzyme based on its purification, molecular cloning, three-dimensional structure, and functional deletion in mice. IL-1β is a major mediator of inflammatory disease. IL-1β is synthesized as an inactive 31-kDa precursor protein (pIL-1β). The precursor is cleaved by a highly specific proteinase, termed IL-1β converting enzyme (ICE). The discovery of ICE, a unique processing enzyme involved in the production of active IL-1β, provides a new approach to specifically block the production of this potent cytokine. ICE is a cysteine proteinase that cleaves pIL-1β twice within the prodomain at aspartic acid residues. The development of potent inhibitors based on the unique substrate specificity of ICE and genetically engineered mice deficient in the enzyme confirms the importance of the enzyme in pIL-1β processing and suggests that inhibitors of the enzyme may be useful in the treatment of inflammatory disease. The discovery and development of inhibitors against the enzyme hold great promise therapeutically. Potent inhibitors of the enzyme are useful in the treatment of a number of important inflammatory diseases and potentially in the management of leukemia.