SUMOylation of optineurin is critical for inhibiting interferon β production

Abstract

Targeting the vital kinase protein TBK1, optineurin (OPTN) performs as a suppressor involved in controlling RNA virus-induced interferon β (IFN-β) production. It has been determined that OPTN is altered by phosphorylation and ubiquitination, which are crucial for the generation of IFN-β and mitophagy. In this study, endogenous OPTN was first discovered in human cells at a molecular mass of about 115 kD. The SUMOylation band was verified to be the higher molecular mass band of the OPTN. Additionally, the OPTN SUMOylation band was seen in cells from several species, including mouse, rabbit, bovine, porcine, etc., but not in cells from avian animals (chicken and duck). This finding suggests that OPTN SUMOylation is well conserved in mammals but not in avian animals. Additionally, it was determined that some lysine residues in the human OPTN had SUMOylation sites that followed the consensus motif. LPS, VSV infection, starvation, and RNA virus infection are a few of the stimuli that encourage endogens OPTN SUMOylation. OPTN SUMOylation is essential for OPTN biological activity, as evidenced by the stark differences in the cellular distribution of mutant OPTN SUMOylation sites from wild type (WT) OPTN. Additionally, we discovered that non-SUMOylated OPTN lost its ability to block both IFN-β production. Our findings offer a preliminary understanding of how OPTN SUMOylation regulates IFN-β production.