VIB Center for Inflammation Research, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium.
VIB Center for Inflammation Research, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium.
Trends Immunol. 2021 Jul;42(7):590-603. doi: 10.1016/j.it.2021.05.003. Epub 2021 May 29.
Tight control of inflammatory signaling pathways is an absolute requirement to avoid chronic inflammation and disease. One of the proteins responsible for such control is OTU deubiquitinase with linear linkage specificity (OTULIN), the only mammalian deubiquitinating enzyme (DUB) exclusively hydrolyzing linear ubiquitin chains from proteins modified by the linear ubiquitin chain assembly complex (LUBAC) described thus far. Recent findings show that loss-of-function mutations in OTULIN underlie a severe early-onset human autoinflammatory disease and severe pathology in experimental mouse models. Here, we review the molecular and cellular mechanisms by which OTULIN controls inflammation and discuss the involvement of OTULIN in inflammatory disease development. We also highlight several newly identified roles for OTULIN, including a ubiquitin-independent function.
严格控制炎症信号通路是避免慢性炎症和疾病的绝对要求。负责这种控制的蛋白质之一是具有线性连接特异性的 OTU 去泛素化酶 (OTULIN)，它是迄今为止唯一的哺乳动物去泛素化酶 (DUB)，专门水解由线性泛素链组装复合物 (LUBAC) 修饰的蛋白质上的线性泛素链。最近的研究结果表明，OTULIN 的功能丧失突变是一种严重的早发性人类自身炎症性疾病和实验性小鼠模型中严重病理学的基础。在这里，我们回顾了 OTULIN 控制炎症的分子和细胞机制，并讨论了 OTULIN 参与炎症性疾病发展的情况。我们还强调了 OTULIN 的几个新发现的作用，包括一个非泛素依赖的功能。
