Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis

作者：Ronald Allan M. Panganiban, Hae‐Ryung Park, Maoyun Sun, Maya Shumyatcher, Blanca E. Himes, Quan Lu · 发表于：Proceedings of the National Academy of Sciences · 年份：2019 · DOI：10.1073/pnas.1906275116 · 被引用次数：72 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Genetics and Neurodevelopmental Disorders

Significance Dysregulated endoplasmic reticulum (ER) stress response contributes to the pathogenesis of myriad diseases. The molecular pathways leading to ER stress-induced cell death are well characterized; however, much less is known about how cells suppress excessive ER stress response to avoid apoptosis and restore homeostasis. Using a CRISPR-based loss-of-function genetic screen, our study uncovered multiple suppressors of ER stress response. These suppressors include a polycomb protein complex that directly inhibits the expression of the transcriptional factor central to ER stress-induced cell death and a microRNA that targets IRE1, a canonical ER stress pathway component. Our study reveals regulatory mechanisms that ameliorate potentially damaging stress response and provides potential therapeutic targets for pathologies whose etiology is linked to overactive ER stress response.