SUMOylation of PES1 upregulates its stability and function via inhibiting its ubiquitination.
SUMOylation of PES1 upregulates its stability and function via inhibiting its ubiquitination.
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PES1 的 SUMO 化通过抑制其泛素化来上调其稳定性和功能
DOI：
10.18632/oncotarget.10494
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Li S;Wang M;Qu X;Xu Z;Yang Y;Su Q;Wu H
PES1 是 PeBoW 复合体的组成部分，是 28S 和 5.8S 核糖体 RNA 成熟以及 60S 核糖体形成所必需的。核糖体生物发生的失调可能导致致癌。在这项研究中，我们发现PES1可以被小泛素样修饰剂（SUMO）SUMO-1、SUMO-2和SUMO-3修饰，并且PES1的SUMO化受到雌激素（E2）的刺激。在 PES1 的 C 端富含 Glu 的结构域中发现了一个主要的 SUMO 化位点 (K517)。用精氨酸取代 K517 消除了 PES1 的 SUMO 化。 SUMOylation 还通过抑制 PES1 的泛素化来稳定 PES1。此外，PES1 SUMO化正向调节雌激素信号通路。 SUMO化通过增加 ERα 的稳定性，增强 PES1 促进雌激素受体 α (ERα) 介导的转录的能力，无论 E2 存在还是不存在。此外，PES1的SUMO化还增加了细胞周期中S期细胞的比例，并在体外和体内促进乳腺癌细胞的增殖。这些发现表明，SUMO化对PES1的翻译后修饰可能是调节PES1体内功能的关键因素。
PES1 is a component of the PeBoW complex, which is required for the maturation of 28S and 5.8S ribosomal RNAs, as well as for the formation of the 60S ribosome. Deregulation of ribosomal biogenesis can contribute to carcinogenesis. In this study, we showed that PES1 could be modified by the small ubiquitin-like modifier (SUMO) SUMO-1, SUMO-2 and SUMO-3, and SUMOylation of PES1 was stimulated by estrogen (E2). One major SUMOylation site (K517) was identified in the C-terminal Glu-rich domain of PES1. Substitution of K517 with arginine abolished the SUMOylation of PES1. SUMOylation also stabilized PES1 through inhibiting its ubiquitination. In addition, PES1 SUMOylation positively regulated the estrogen signaling pathway. SUMOylation enhanced the ability of PES1 to promote estrogen receptor α (ERα)-mediated transcription by increasing the stability of ERα, both in the presence and absence of E2. Moreover, SUMOylation of PES1 also increased the proportion of S-phase cells in the cell cycle and promoted the proliferation of breast cancer cells both in vitro and in vivo. These findings showed that posttranslational modification of PES1 by SUMOylation may serve as a key factor that regulates the function of PES1 in vivo.