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

Nature volume 356, pages 768–774 (1992)Cite this article

Abstract

Interleukin-1β (IL-1β)-converting enzyme cleaves the IL-1β precursor to mature IL-1β, 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-lβ-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-1β, indicating that it is a potential therapeutic target.

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Authors and Affiliations

  1. Department of Biochemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Nancy A. Thornberry, Herbert G. Bull & Erin P. Gaffney

  2. Department of Biochemical and Molecular Pathology, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Jimmy R. Calaycay, Andrew D. Howard, Douglas K. Miller, Jeffrey R. Weidner, Julia M. Ayala, Gloria J.-F. Ding, Linda A. Egger, Oksana C. Palyha, S. M. Raju, J. Paul Salley, Ting-Ting Yamin, Richard A. Mumford & John A. Schmidt

  3. Department of Medicinal Chemical Research, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Kevin T. Chapman & Malcolm MacCross

  4. Department of Cellular and Molecular Pharmacology, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Matthew J. Kostura, Jayne Chin & Guadalupe Limjuco

  5. Department of Molecular Immunology, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Susan M. Molineaux, Francesca J. Casano, Anna M. Rolando & Michael J. Tocci

  6. Department of Biochemical Process Research and Development, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    John Aunins

  7. Department of Biological Data, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065, USA

    Keith O. Elliston

  8. Beckman Research Institute City of Hope, 1450 East Duarte Road, Duarte, California, 91010, USA

    Terry D. Lee & John E. Shively

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

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