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Intracellular interleukin (IL)-1 family cytokine processing enzyme

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Abstract

The interleukin (IL)-1 family is the largest family of interleukins. Eleven members of the IL-1 family of ligands are intracellular molecules, except a single isoform of an IL-1 receptor antagonist (IL-1Ra; also known as IL-1RN), which contains a signal peptide at the N-terminus for effective secretion. The inflammasome is a complex of intracellular molecules that is responsible for the processing of IL-1β and IL-18, whereas the remaining IL-1 family members, including IL-1α, are processed in an inflammasome caspase-1-independent pathway. Among the eleven members of the IL-1 family ligands, precursor IL-1α, IL-1β, and IL-33 have comparatively long pro-peptides of approximately 110 amino acid residues at the N-terminus. However, the other IL-1 members, except for IL-37 (also known as IL-1F7), have relatively short propeptides with fewer than 40 amino acid residues at the N-terminus. Most cytokines, including interferons and interleukins, possess a hydrophobic signal sequence for secretion. Therefore, soluble cytokines readily act on cell surface receptors immediately after their release from cells. Unlike other cytokine families, IL-1 family ligands exhibit two-step regulation: transcriptional induction at the mRNA level and post-translational modification at the protein level because of the lack of a hydrophobic signal sequence at the N-terminus. Various processing enzymes involved in the activation of intracellular IL-1 family cytokines likely provide effective immune regulation to protect the host from infections. In this review, we describe all eleven IL-1 family ligand processing enzymes, mature ligand functions, and mode of receptor conformation.

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This paper was supported by Konkuk University in 2014.

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    1. Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea

      Areum Kwak & Soohyun Kim

    2. College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea

      Areum Kwak & Soohyun Kim

    3. Department of Medicine, Pusan Paik Hospital, College of Medicine, Inje University, Busan, 47392, Korea

      Youngmin Lee

    4. Division of Nephrology, Department of Internal Medicine, Jeju National University, Jeju-Si, Jeju-Do, 63243, Korea

      Hyunwoo Kim

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    Areum Kwak and Youngmin Lee have contributed equally to this work.

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    Kwak, A., Lee, Y., Kim, H. et al. Intracellular interleukin (IL)-1 family cytokine processing enzyme. Arch. Pharm. Res. 39, 1556–1564 (2016). https://doi.org/10.1007/s12272-016-0855-0

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