title: Emergence of the A20/ABIN-mediated inhibition of NF-κB signaling via modifying the ubiquitinated proteins in a basal chordate.
abstract: In the past decade, ubiquitination has been well documented to have multifaceted roles in regulating NF-κB activation in mammals. However, its function, especially how deubiquitinating enzymes balance the NF-κB activation, remains largely elusive in invertebrates. Investigating bbtA20 and its binding proteins, bbt A20-binding inhibitor of NF-κB (bbtABIN1) and bbtABIN2, in Chinese amphioxus Branchiostoma belcheri tsingtauense, we found that bbtABIN2 can colocalize and compete with bbt TNF receptor-associated factor 6 to connect the K63-linked polyubiquitin chains, whereas bbtABIN1 physically links bbtA20 to bbt NF-κB essential modulator (bbtNEMO) to facilitate the K48-linked ubiquitination of bbtNEMO. Similar to human A20, bbtA20 is a dual enzyme that removes the K63-linked polyubiquitin chains and builds the K48-linked polyubiquitin chains on bbt receptor-interacting serine/threonine protein kinase 1b, leading to the inhibition of NF-κB signaling. Our study not only suggests that ubiquitination is an ancient strategy in regulating NF-κB activation but also provides the first evidence, to our knowledge, for ABINs/A20-mediated inhibition of NF-κB via modifying the ubiquitinated proteins in a basal chordate, adding information on the stepwise development of vertebrate innate immune signaling.
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.
authors.forename: Shaochun
authors.initials: S
authors.lastname: Yuan
authors.forename: Xiangru
authors.initials: X
authors.lastname: Dong
authors.forename: Xin
authors.initials: X
authors.lastname: Tao
authors.forename: Liqun
authors.initials: L
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Ruan
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D064175:Lancelets / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D057149:Ubiquitinated Proteins; D044767:Ubiquitin-Protein Ligases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
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