A conserved AAA+ ATPase network regulates endoplasmic reticulum stress-induced transcription

In C. elegans cdc-48.2(-/-) mutant animals, ER stress-mediated expression of the UPR ckb-2::GFP reporter transgene is abolished. Here, we have used this phenotype in a genome-wide RNAi screen to identify genes involved in the CDC-48.2 mediated ER stress transcription. Combined with a comparative proteomic analysis, this approach has allowed us to identify the AAA+ ATPase RUVB-2 as a novel regulator of the ER stress response and a CDC-48 degradation target.

在秀丽隐杆线虫（C. elegans）的cdc-48.2(-/-)突变体动物中，内质网应激（ER stress）介导的未折叠蛋白反应（UPR）报告转基因ckb-2::GFP的表达被完全消除。本研究借助该表型开展全基因组RNA干扰（RNAi）筛选，以鉴定参与CDC-48.2介导的内质网应激转录过程的基因。结合比较蛋白质组学分析，该研究策略成功使我们鉴定出AAA+ ATP酶（AAA+ ATPase）RUVB-2，其可作为内质网应激应答的新型调控因子，同时亦是CDC-48的降解靶点。