SUMO proteins are important regulators of many key cellular functions in part through their ability to form interactions with other proteins containing SUMO interacting motifs (SIMs). One characteristic feature of all SUMO proteins is the presence of a highly divergent intrinsically disordered region at their N-terminus. In this study, we examine the role of this N-terminal region of SUMO proteins in SUMO–SIM interactions required for the formation of nuclear bodies by the promyelocytic leukemia (PML) protein (PML-NBs). We demonstrate that the N-terminal region of SUMO1 functions in a paralog specific manner as an auto-inhibition domain by blocking its binding to the phosphorylated SIMs of PML and Daxx. Interestingly, we find that this auto-inhibition in SUMO1 is relieved by zinc, and structurally show that zinc stabilizes the complex between SUMO1 and a phospho-mimetic form of the SIM of PML. In addition, we demonstrate that increasing cellular zinc levels enhances PML-NB formation in senescent cells. Taken together, these results provide important insights into a paralog specific function of SUMO1, and suggest that zinc levels could play a crucial role in regulating SUMO1-SIM interactions required for PML-NB formation and function.

中文翻译：

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锌通过调节 SUMO1 中的旁系同源物特异性自抑制来控制 PML 核体的形成

SUMO 蛋白是许多关键细胞功能的重要调节剂，部分原因在于它们能够与其他含有 SUMO 相互作用基序 (SIM) 的蛋白质形成相互作用。所有 SUMO 蛋白的一个特征是在它们的 N 端存在高度不同的内在无序区域。在这项研究中，我们检查了 SUMO 蛋白的 N 末端区域在早幼粒细胞白血病 (PML) 蛋白 (PML-NBs) 形成核体所需的 SUMO-SIM 相互作用中的作用。我们证明了 SUMO1 的 N 末端区域通过阻断其与 PML 和 Daxx 的磷酸化 SIM 的结合以旁系同源物特异性方式作为自动抑制域发挥作用。有趣的是，我们发现 SUMO1 的这种自动抑制被锌所缓解，并且在结构上表明锌稳定了 SUMO1 和 PML SIM 的磷模拟形式之间的复合物。此外，我们证明增加细胞锌水平会增强衰老细胞中 PML-NB 的形成。总之，这些结果为 SUMO1 的旁系同源物特定功能提供了重要的见解，并表明锌水平可以在调节 PML-NB 形成和功能所需的 SUMO1-SIM 相互作用中发挥关键作用。