Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
Cell Death Dis. 2023 Oct 10;14(10):659. doi: 10.1038/s41419-023-06183-3.
Linear ubiquitination is a specific post-translational modification in which ubiquitin is linked through M1 residue to form multiple types of polyubiquitin chains on substrates in order to regulate cellular processes. LUBAC comprised by HOIP, HOIL-1L, and SHARPIN as a sole E3 ligase catalyzes the generation of linear ubiquitin chains, and it is simultaneously adjusted by deubiquitinases such as OTULIN and CYLD. Several studies have shown that gene mutation of linear ubiquitination in mice accompanied by different modalities of cell death would develop relative diseases. Cell death is a fundamental physiological process and responsible for embryonic development, organ maintenance, and immunity response. Therefore, it is worth speculating that linear ubiquitin mediated signaling pathway would participate in different diseases. The relative literature search was done from core collection of electronic databases such as Web of Science, PubMed, and Google Scholar using keywords about main regulators of linear ubiquitination pathway. Here, we summarize the regulatory mechanism of linear ubiquitination on cellular signaling pathway in cells with apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Intervening generation of linear ubiquitin chains in relative signaling pathway to regulate cell death might provide novel therapeutic insights for various human diseases.
线性泛素化是一种特定的翻译后修饰，其中泛素通过 M1 残基连接，在底物上形成多种类型的多泛素链，以调节细胞过程。由 HOIP、HOIL-1L 和 SHARPIN 组成的 LUBAC 作为唯一的 E3 连接酶催化线性泛素链的生成，同时受到 OTULIN 和 CYLD 等去泛素酶的调节。一些研究表明，小鼠线性泛素化基因突变伴随着不同形式的细胞死亡会发展出相对应的疾病。细胞死亡是一种基本的生理过程，负责胚胎发育、器官维持和免疫反应。因此，可以推测线性泛素介导的信号通路可能参与了不同的疾病。相对文献检索是从 Web of Science、PubMed 和 Google Scholar 等电子数据库的核心集合中使用关于线性泛素化途径主要调节剂的关键词进行的。在这里，我们总结了线性泛素化对细胞凋亡、细胞坏死、自噬、细胞焦亡和铁死亡中细胞信号通路的调节机制。干预相对信号通路中线性泛素链的生成以调节细胞死亡可能为各种人类疾病提供新的治疗思路。
