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

Nancy A. Thornberry; Herbert G. Bull; Jimmy Calaycay; Kevin T. Chapman; Andrew Howard; Matthew J. Kostura; Douglas K. Miller; Susan M. Molineaux; Jeffrey R. Weidner; John Auniņš; Keith Elliston; Julia M. Ayala; Francesca J. Casano; Jayne Chin; G J Ding; Linda A. Egger; Erin P. Gaffney; G Limjuco; Oksana Palyha; S Raju; Anna Rolando; J. Paul Salley; Ting-Ting Yamin; Terry D. Lee; John E. Shively; Malcolm MacCross; Richard A. Mumford; John A. Schmidt; Michael J. Tocci

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.

Keywords

EnzymeProteaseCysteineBETA (programming language)BiochemistryCysteine proteaseChemistryPeptideCloning (programming)Molecular biologyBiology

MeSH Terms

Amino Acid SequenceBase SequenceBindingCompetitiveCaspase 1ChromatographyAffinityChromatographyDEAE-CelluloseChromatographyHigh Pressure LiquidChromosome MappingCloningMolecularDiazomethaneElectrophoresisPolyacrylamide GelHumansInterleukin-1MetalloendopeptidasesMolecular Sequence DataMonocytesOpen Reading FramesProtein ProcessingPost-TranslationalSequence HomologyNucleic AcidSubstrate Specificity

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Publication Info

Year: 1992
Type: article
Volume: 356
Issue: 6372
Pages: 768-774
Citations: 2546
Access: Closed

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APA Style

                            
                                
                                    Nancy A. Thornberry, 
                                
                                    Herbert G. Bull, 
                                
                                    Jimmy Calaycay
                                
                                et al.
                            
                            (1992). 
                            A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes. 
                            Nature
                            , 356
                            (6372)
                            , 768-774.
                            https://doi.org/10.1038/356768a0
                        

Identifiers

DOI: 10.1038/356768a0
PMID: 1574116

Data Quality

Data completeness: 81%