Advances in the Study of the Ubiquitin-Editing Enzyme A20

Abstract

Ubiquitin modification is a common post-translational protein modification and an important mechanism whereby the body regulates protein levels and functions. As a common enzyme associated with ubiquitin modification, the ubiquitin-editing enzyme A20 may be closely associated with the development of numerous pathological processes through its different structural domains. The aim of this paper is to provide an overview of the following: advances in ubiquitination research, the structure and function of A20, and the relationships between A20 and immune inflammatory response, apoptosis, necroptosis, pyroptosis, and autophagy.

WITHDRAWN: Acute cerebral infarction patients' 3-month mortality predicted by peripheral tumor necrosis factor alpha-induced protein 3 mRNA level

“…A20 had a protective effect on the injured endothelium and improved the neurological de cits in middle cerebral artery occlusion/reperfusion rats. Second, A20 could inhibit NF-κB activation through the TNF-α, TLR4, nucleotide binding oligomer domain, T cell B, and IL-17 pathways, thereby inhibiting NF-κB transcription in the cytoplasm and downstream in ammatory factors to reduce the in ammatory response 31 . Furthermore, A20 is antiin ammatory in Endothelial Cell (EC )) and SMC through its ability to concomitantly inhibit NF-κB activation in response to in ammatory (TNF), immune (CD40), and oxidative insults and interrupt atherogenic interferon gamma (IFNγ) signaling 32 , A20/ Tumor necrosis factor alpha induced protein (TNFAIP3) Increases ENOS Expression in an ERK5Dependent Manner to Support Health in the Face of In ammation 32 .…”

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

“…In an AR mouse model, antigen invasions, including OVA or pathogens, triggered pathogen recognition receptors, including TLRs, inducing A20 expression at both mRNA and protein levels (24). Subsequently, A20 plays a role in a negative feedback loop by inhibiting key pro-inflammatory signaling pathways, including those controlling NF-kB signaling (11,22). Hu et al reported that intranasal administration of an over-expression vector which could cause simultaneous overexpression of a dust mite antigen, dermatophagoides pteronyssinus (Der p) 2, along with A20 protein in a mouse AR model, led to significantly enhanced infiltration of mononuclear cells in the nasal mucosa, and attenuated the levels of Der p2−specific IgE, IL−4, and IL−13 in serum (24).…”

“…A20, encoded by the TNFAIP3 gene, is a cytoplasmic ubiquitin (Ub)-modifying enzyme with dual ubiquitinating and deubiquitinating (DUB) activities ( 11 ). It acts as an endogenous negative regulator of NF-κB signaling and has anti-inflammatory and immunomodulatory effects in various inflammatory and autoimmune diseases ( 12 ).…”

“…This phenomenon was confirmed in an allergic-asthma mouse model, where NF-kB translocation blockade led to decreased interleukin (IL)-4 and IL-17 production by type 2 helper T (Th2) and Th17 cells, respectively (10). A20, encoded by the TNFAIP3 gene, is a cytoplasmic ubiquitin (Ub)-modifying enzyme with dual ubiquitinating and deubiquitinating (DUB) activities (11). It acts as an endogenous negative regulator of NF-kB signaling and has anti-inflammatory and immunomodulatory effects in various inflammatory and autoimmune diseases (12).…”

“…2 Regulation of A20 and its relationship to NF-kB signaling in allergic disease A20 is a highly conserved protein that comprising an aminoterminal ovarian tumor domain (OTU) at its N-terminus, and seven zinc finger (ZnF) domains at its C-terminus (11). The OTU domain is responsible for mediating deubiquitinating (DUB) activity, while ZnF4 and ZnF7 domains are responsible for K63and M1-linked ubiquitination, respectively, thereby contributing to A20 ubiquitinating activity (12,22).…”