HSPBP1 通过抑制 RIG-I 的 K48 连接泛素化促进细胞 RLR 介导的抗病毒反应。
HSPBP1 facilitates cellular RLR-mediated antiviral response by inhibiting the K48-linked ubiquitination of RIG-I.
机构信息
Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi, 330022, China.
Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi, 330022, China.
出版信息
Mol Immunol. 2021 Jun;134:62-71. doi: 10.1016/j.molimm.2021.03.002. Epub 2021 Mar 10.
Retinoic acid-inducible gene I (RIG-I) plays a critical role in the recognition of intracytoplasmic viral RNA. Upon binding to the RNA of invading viruses, the activated RIG-I translocates to mitochondria, where it recruits adapter protein MAVS, causing a series of signaling cascades. In this study, we demonstrated that Hsp70 binding protein 1 (HSPBP1) promotes RIG-I-mediated signal transduction. The overexpression of HSPBP1 can increase the stability of RIG-I protein by inhibiting its K48-linked ubiquitination, and promote the activation of IRF3 and the production of IFN-β induced by Sendai virus. Knockdown and knockout of HSPBP1 leads to down-regulation of virus-induced RIG-I expression, inhibits IRF3 activation, and reduces the production of IFNB1. These results indicate that HSPBP1 positively regulates the antiviral signal pathway induced by inhibiting the K48-linked ubiquitination of RIG-I.
视黄酸诱导基因 I（RIG-I）在识别细胞内病毒 RNA 方面发挥着关键作用。在与入侵病毒的 RNA 结合后，激活的 RIG-I 易位到线粒体，在那里它招募衔接蛋白 MAVS，引发一系列信号级联反应。在这项研究中，我们证明了热休克蛋白 70 结合蛋白 1（HSPBP1）促进 RIG-I 介导的信号转导。HSPBP1 的过表达可以通过抑制其 K48 连接的泛素化来增加 RIG-I 蛋白的稳定性，并促进仙台病毒诱导的 IRF3 和 IFN-β 的产生。HSPBP1 的敲低和敲除导致病毒诱导的 RIG-I 表达下调，抑制 IRF3 激活，并减少 IFNB1 的产生。这些结果表明 HSPBP1 通过抑制 RIG-I 的 K48 连接泛素化来正向调节抗病毒信号通路。
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