Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'
Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'
复制标题
DOI：
10.1038/sj.emboj.7601490
复制
发表时间：
2007-01-10
期刊：
影响因子：
11.4
通讯作者：
Nakajima, Toshihiro
中科院分区：
文献类型：
--
作者：
Yamasaki, Satoshi;Yagishita, Naoko;Nakajima, Toshihiro
滑膜蛋白，也称为HRD 1，是一种E3泛素连接酶，参与内质网相关的降解。在哺乳动物中，滑膜小提琴在各种生理和病理过程中起着至关重要的作用，包括胚胎发育和关节病的发病机制。然而，人们对Synoviolin在这些作用中的分子机制知之甚少。为了澄清这些问题，我们分析了滑膜素无效细胞中的蛋白质表达谱。在这里，我们报告，滑膜蛋白靶向肿瘤抑制基因p53的泛素化。滑膜素在细胞质中螯合和代谢p53，并负调节其细胞水平和生物学功能，包括转录、细胞周期调节和凋亡。此外，这些p53的调节功能的滑膜蛋白是无关的其他E3泛素连接酶的p53，如MDM 2，Pirh 2和Cop1，形成自动调节反馈回路。我们的研究结果提供了新的见解p53信号介导的Synoviolin。
Synoviolin, also called HRD1, 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. Here, we report 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.