Discovery of a Compound That Inhibits IRE1α <i>S</i>-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress.

ABSTRACT: Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes S-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, S-nitrosylation of IRE1α compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the S-nitrosylation of IRE1α by targeting nitrosylated cysteine residues. We ultima

SUBMITTER: Kurogi H 

PROVIDER: S-EPMC11667674 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature