Crosstalk between ER stress and p53 pathway

紫草素是一种E3泛素连接酶，与内质网相关的降解有关。在哺乳动物中，突触素在多种生理和病理过程中发挥着重要作用，包括胚胎发生和关节病的发病机制。然而，关于雪诺紫素在这些作用中的分子机制还知之甚少。为了阐明这些问题，我们分析了突触素缺失细胞的蛋白质表达谱。因此，我们发现赛诺维林针对肿瘤抑制基因P53进行泛素化。赛诺维林在细胞质中隔离和代谢P53，负调控P53的细胞水平和生物学功能，包括转录、细胞周期调节和细胞凋亡。此外，Synoviin的这些P53调节功能与P53的其他E3泛素连接酶如MDM2、Pirh2和Cop1无关，它们形成自我调节反馈环。我们的结果为研究由赛诺维林介导的P53信号通路提供了新的见解。

Synoviolin is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum-associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Hereby, we found that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.