Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.

中文翻译：

---

抗氧化酶蛋氨酸亚砜还原酶A（MsrA）与Jab1 / CSN5相互作用并调节其功能。

蛋氨酸亚砜（MetO）是一种氧化后翻译修饰，主要发生在氧化应激条件下，导致蛋白质结构和功能的改变。该修饰通过进化上保守的蛋氨酸亚砜还原酶（Msr）系统的MetO还原来调节。Msr A型酶（MsrA）作为细胞抗氧化剂发挥重要作用，并促进细胞存活。由c-Jun激活结构域结合蛋白1（Jab1）控制的泛素-（Ub）样腺苷酸化途径也影响细胞存活。Jab1通过结合和靶向P27泛素化和降解来负调控细胞周期抑制剂细胞周期蛋白依赖性激酶抑制剂1B（P27）的表达。在这里我们报告发现，MsrA与Jab1相互作用并增强Jab1的树突化酶活性（Nedd8的去除）。反过来，观察到树突状的Cullin-1（Cul-1，E3 Ub连接酶复合物的一个组成部分）的水平增加。此外，MsrA的作用增加了Jab1对P27的结合亲和力，而MsrA消融引起P27表达的急剧增加。因此，提出了MsrA和Jab1之间的相互作用对Jab1的功能具有积极作用，并用作调节细胞对氧化应激的抗性并增强细胞存活的手段。而MsrA切除会导致P27表达急剧增加。因此，提出了MsrA和Jab1之间的相互作用对Jab1的功能具有积极作用，并用作调节细胞对氧化应激的抗性并增强细胞存活的手段。而MsrA切除会导致P27表达急剧增加。因此，提出了MsrA和Jab1之间的相互作用对Jab1的功能具有积极作用，并用作调节细胞对氧化应激的抗性并增强细胞存活的手段。