Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
George Williams Hooper Foundation, University of California, San Francisco, San Francisco, CA, USA.
Life Sci Alliance. 2021 Oct 11;4(12). doi: 10.26508/lsa.202101247. Print 2021 Dec.
The intracellular bacterial pathogen () secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this -dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.
胞内细菌病原体 () 将约 330 种效应蛋白分泌到宿主细胞中，以塑造内质网衍生的复制龛位。我们之前报道了五种 () 效应蛋白可以抑制内质网未折叠蛋白反应 (UPR) 途径的关键传感器 IRE1。在这项研究中，我们发现了一组 () 毒素，它们选择性地激活 UPR 传感器 ATF6，导致其切割、核易位和靶基因转录。与传统模型不同的是，这种 () 依赖的 ATF6 激活不需要其运输到高尔基体或其被 S1P/S2P 蛋白酶切割。我们认为，我们的发现强调了 () 对三种 UPR 传感器施加的独特调控控制，并扩展了选择性扰乱宿主稳态途径的细菌蛋白的 repertoire。
