Intracellular interleukin (IL)-1 family cytokine processing enzyme.
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.
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.|College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
Areum
A
Kwak
Department of Medicine, Pusan Paik Hospital, College of Medicine, Inje University, Busan, 47392, Korea.
Youngmin
Y
Lee
Division of Nephrology, Department of Internal Medicine, Jeju National University, Jeju-Si, Jeju-Do, 63243, Korea.
Hyunwoo
H
Kim
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea. soohyun@konkuk.ac.kr.|College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea. soohyun@konkuk.ac.kr.
Soohyun
S
Kim
D000595:Amino Acid Sequence; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D007375:Interleukin-1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D017472:Receptors, Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D058847:Inflammasomes; D007375:Interleukin-1; D008024:Ligands; D017472:Receptors, Interleukin-1; D020170:Caspase 1
Caspase-1; Inflammasome; Inflammation; Interleukin-1 family cytokine; Interleukin-1 family cytokine receptor