Molecular Characterization and Expression Analysis of Tumor Necrosis Factor Alpha-induced Protein 3 (TNFAIP3/A20) Gene from Japanese Pufferfish &lt;i&gt;Takifugu rubripes&lt;/i&gt;

Hikima, Jun-ichi; Morita, Misaki; Kinoshita, Susumu; Basu, Madhubanti; Biswas, Gouranga; Kono, Tomoya; Sakai, Masahiro

doi:10.3147/jsfp.52.15

Cited by 4 publications

(1 citation statement)

References 23 publications

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“…Orthologs of human A20 have been identified in several fish species, including zebrafish ( Danio rerio ) [ 29 ], fathead minnow ( Pimephales promelas ) [ 30 ], and Japanese pufferfish ( Takifugu rubripes ) [ 31 ]. Fish A20s, such as those of mammals, might play a key role in maintaining inflammatory homeostasis.…”

Section: Introductionmentioning

confidence: 99%

A20 Inhibits LPS-Induced Inflammation by Regulating TRAF6 Polyubiquitination in Rainbow Trout

Jang

Kim

Jung

et al. 2021

IJMS

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The ubiquitin-editing enzyme A20 is known to inhibit the NF-κB transcription factor in the Toll-like receptor (TLR) pathways, thereby negatively regulating inflammation. However, its role in the TLR signaling pathway in fish is still largely unknown. Here, we identified a gene encoding A20 (OmA20) in rainbow trout, Oncorhynchus mykiss, and investigated its role in TLR response regulation. The deduced amino acid sequence of OmA20 contained a conserved N-terminal ovarian tumor (OTU) domain and seven C-terminal zinc-finger (ZnF) domains. Lipopolysaccharide (LPS) stimulation increased OmA20 expression in RTH-149 cells. In LPS-stimulated RTH-149 cells, gain- and loss-of-function experiments revealed that OmA20 inhibited MAPK and NF-κB activation, as well as the expression of pro-inflammatory cytokines. OmA20 interacted with TRAF6, a key molecule involved in the activation of TLR-mediated NF-κB signaling pathways. LPS treatment increased the K63-linked polyubiquitination of TRAF6 in RTH-149 cells, which was suppressed when OmA20 was forced expression. Furthermore, mutations in the OTU domain significantly decreased deubiquitination of the K63-linked ubiquitin chain on TRAF6, indicating that deubiquitinase activity is dependent on the OTU domain. These findings suggest that OmA20, like those of mammals, reduces LPS-induced inflammation in rainbow trout, most likely by regulating K63-linked ubiquitination of TRAF6.

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Section: Introductionmentioning

confidence: 99%