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A20的非催化泛素结合可预防银屑病关节炎样疾病和炎症
作者:小柯机器人 发布时间:2020/3/24 10:37:15

美国加州大学旧金山分校Averil Ma、Barbara A. Malynn等研究人员合作发现,A20的非催化泛素结合可预防银屑病关节炎样疾病和炎症。2020年3月16日,《自然—免疫学》杂志在线发表了这项成果。

研究人员发现表达A20锌指7(ZF7)泛素结合基序三个不同靶向突变的小鼠均产生了具有银屑病关节炎常见特征的指状关节炎,而在A20的OTU或ZF4基序中表达点突变的小鼠则没有这种表型 。A20ZF7小鼠的关节炎需要T细胞和MyD88,对肿瘤坏死因子和白介素17A非常敏感,并在无菌条件下持续存在。A20ZF7细胞表现出持续的IκB激酶活性,从而在体内外导致晚期核因子-κB响应基因的转录过度。此外,在A20的ZF4和ZF7基序中表达双突变型A20蛋白的小鼠在围产期死于多器官炎症。因此,A20的ZF4和ZF7基序以非催化方式协同预防炎症性疾病。

据介绍,A20是一种抗炎蛋白,与人类疾病密切相关。

附:英文原文

Title: Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis–like disease and inflammation

Author: Bahram Razani, Michael I. Whang, Francis S. Kim, Mary C. Nakamura, Xiaofei Sun, Rommel Advincula, Jessie A. Turnbaugh, Mihir Pendse, Priscilia Tanbun, Philip Achacoso, Peter J. Turnbaugh, Barbara A. Malynn, Averil Ma

Issue&Volume: 2020-03-16

Abstract: A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20’s zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20’s OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20ZF7 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20ZF7 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20’s ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20’s ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.

DOI: 10.1038/s41590-020-0634-4

Source: https://www.nature.com/articles/s41590-020-0634-4

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex