Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines

Rebecca L Ambrose; Aaron M Brice; Alessandro T Caputo; Marina R Alexander; Leon Tribolet; Yu Chih Liu; Timothy E Adams; Andrew G D Bean; Cameron R Stewart

doi:10.1016/j.heliyon.2020.e04115

Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines

Heliyon. 2020 Jun 3;6(6):e04115. doi: 10.1016/j.heliyon.2020.e04115. eCollection 2020 Jun.

Authors

Rebecca L Ambrose¹, Aaron M Brice¹, Alessandro T Caputo², Marina R Alexander¹, Leon Tribolet¹, Yu Chih Liu², Timothy E Adams², Andrew G D Bean¹, Cameron R Stewart¹

Affiliations

¹ CSIRO Health & Biosecurity, Australian Centre for Disease Preparedness, Geelong, Victoria, 3220, Australia.
² CSIRO Manufacturing, Parkville, Victoria, 3010, Australia.

Abstract

Regulation of type-I interferon (IFN) production is essential to the balance between antimicrobial defence and autoimmune disorders. The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domains, previously C6orf106) was recently characterised as an inhibitor of antiviral and proinflammatory cytokine (interferon-alpha/beta and tumor necrosis factor alpha) transcription. Currently there is a paucity of information about the molecular characteristics of ILRUN, despite it being associated with several diseases including virus infection, coronary artery disease, obesity and cancer. Here, we characterise ILRUN as a highly phylogenetically conserved protein containing UBA-like and a NBR1-like domains that are both essential for inhibition of type-I interferon and tumor necrosis factor alpha) transcription in human cells. We also solved the crystal structure of the NBR1-like domain, providing insights into its potential role in ILRUN function. This study provides critical information for future investigations into the role of ILRUN in health and disease.

Keywords: Biochemistry; Biomolecules; C6orf106; CBP; ILRUN; Immune response; Immunolgy; Infectious disease; Inflammation; Innate immunity; Interferon; Viruses; p300.