title: A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
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.
authors.affiliation: Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
authors.forename: N A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: H G
authors.initials: HG
authors.lastname: Bull
authors.forename: J R
authors.initials: JR
authors.lastname: Calaycay
authors.forename: K T
authors.initials: KT
authors.lastname: Chapman
authors.forename: A D
authors.initials: AD
authors.lastname: Howard
authors.forename: M J
authors.initials: MJ
authors.lastname: Kostura
authors.forename: D K
authors.initials: DK
authors.lastname: Miller
authors.forename: S M
authors.initials: SM
authors.lastname: Molineaux
authors.forename: J R
authors.initials: JR
authors.lastname: Weidner
authors.forename: J
authors.initials: J
authors.lastname: Aunins
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001667:Binding, Competitive / Q000187:drug effects; D020170:Caspase 1; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003978:Diazomethane / Q000031:analogs & derivatives / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology*; D016366:Open Reading Frames; D011499:Protein Processing, Post-Translational; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity
chemical_list: D007375:Interleukin-1; C015795:diazomethyl ketones; D003978:Diazomethane; D020170:Caspase 1; D008666:Metalloendopeptidases