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IRAK1 依赖性 Regnase-1-14-3-3 复合物形成控制 Regnase-1 介导的 mRNA 降解。

IRAK1-dependent Regnase-1-14-3-3 complex formation controls Regnase-1-mediated mRNA decay.

机构信息

Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

出版信息

Elife. 2021 Oct 12;10:e71966. doi: 10.7554/eLife.71966.

DOI:10.7554/eLife.71966
PMID:34636324
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8553338/
Abstract

Regnase-1 is an endoribonuclease crucial for controlling inflammation by degrading mRNAs encoding cytokines and inflammatory mediators in mammals. However, it is unclear how Regnase-1-mediated mRNA decay is controlled in interleukin (IL)-1β- or Toll-like receptor (TLR) ligand-stimulated cells. Here, by analyzing the Regnase-1 interactome, we found that IL-1β or TLR stimulus dynamically induced the formation of Regnase-1-β-transducin repeat-containing protein (βTRCP) complex. Importantly, we also uncovered a novel interaction between Regnase-1 and 14-3-3 in both mouse and human cells. In IL-1R/TLR-stimulated cells, the Regnase-1-14-3-3 interaction is mediated by IRAK1 through a previously uncharacterized C-terminal structural domain. Phosphorylation of Regnase-1 at S494 and S513 is critical for Regnase-1-14-3-3 interaction, while a different set of phosphorylation sites of Regnase-1 is known to be required for the recognition by βTRCP and proteasome-mediated degradation. We found that Regnase-1-14-3-3 and Regnase-1-βTRCP interactions are not sequential events. Rather, 14-3-3 protects Regnase-1 from βTRCP-mediated degradation. On the other hand, 14-3-3 abolishes Regnase-1-mediated mRNA decay by inhibiting Regnase-1-mRNA association. In addition, nuclear-cytoplasmic shuttling of Regnase-1 is abrogated by 14-3-3 interaction. Taken together, the results suggest that a novel inflammation-induced interaction of 14-3-3 with Regnase-1 stabilizes inflammatory mRNAs by sequestering Regnase-1 in the cytoplasm to prevent mRNA recognition.

摘要

Regnase-1 是一种内切核酸酶，对于哺乳动物通过降解编码细胞因子和炎症介质的 mRNA 来控制炎症至关重要。然而，Regnase-1 介导的 mRNA 降解如何在白细胞介素 (IL)-1β 或 Toll 样受体 (TLR) 配体刺激的细胞中受到控制尚不清楚。在这里，通过分析 Regnase-1 相互作用组，我们发现 IL-1β 或 TLR 刺激动态诱导形成 Regnase-1-β-转导重复蛋白 (βTRCP) 复合物。重要的是，我们还在小鼠和人类细胞中发现了 Regnase-1 和 14-3-3 之间的一种新相互作用。在 IL-1R/TLR 刺激的细胞中，Regnase-1-14-3-3 相互作用是通过 IRAK1 通过一个以前未表征的 C 末端结构域介导的。Regnase-1 的 S494 和 S513 磷酸化对于 Regnase-1-14-3-3 相互作用至关重要，而 Regnase-1 的另一组磷酸化位点已知需要被 βTRCP 和蛋白酶体介导的降解识别。我们发现 Regnase-1-14-3-3 和 Regnase-1-βTRCP 相互作用不是顺序事件。相反，14-3-3 保护 Regnase-1 免受 βTRCP 介导的降解。另一方面，14-3-3 通过抑制 Regnase-1-mRNA 结合来阻止 Regnase-1 介导的 mRNA 降解。此外，Regnase-1 的核质穿梭被 14-3-3 相互作用所阻断。总之，这些结果表明，一种新的炎症诱导的 14-3-3 与 Regnase-1 的相互作用通过将 Regnase-1 隔离在细胞质中来稳定炎症 mRNA，从而防止 mRNA 识别。

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Anal Chem. 2020 Jul 21;92(14):9523-9527. doi: 10.1021/acs.analchem.0c00478. Epub 2020 Jul 6.
2
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Cell. 2020 Apr 30;181(3):621-636.e22. doi: 10.1016/j.cell.2020.03.006. Epub 2020 Apr 6.
3
Toll-like Receptors and the Control of Immunity. toll 样受体与免疫的调控。
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4
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Inflamm Regen. 2024 Mar 15;44(1):14. doi: 10.1186/s41232-024-00326-5.
5
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Adv Exp Med Biol. 2024;1444:145-161. doi: 10.1007/978-981-99-9781-7_10.
6
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7
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8
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9
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6
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10
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