A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes

  • Nature. 1992 Apr 30;356(6372):768-74. doi: 10.1038/356768a0.
N A Thornberry  1 ,  H G Bull ,  J R Calaycay ,  K T Chapman ,  A D Howard ,  M J Kostura ,  D K Miller ,  S M Molineaux ,  J R Weidner ,  J Aunins
Affiliations
  • 1. Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
PMID: 1574116 DOI: 10.1038/356768a0
Abstract

Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine Protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.