MARK2 phosphorylates eIF2α in response to proteotoxic stress

• DOI: 10.1371/journal.pbio.3001096
• Publication Date: 2021-03-11T18:27:41Z
• Authors: Yu-Ning Lu; Sarah Kavianpour; Tao Zhang; Xumei Zhang; Dao Nguyen; Ravi Thombre; Lu He; Jiou Wang
• Keywords: Proteotoxicity; Integrated stress response; eIF2; HSF1; Proteostasis

The regulation of protein synthesis is essential for maintaining cellular homeostasis, especially during stress responses, and its dysregulation could underlie the development human diseases. critical step translation phosphorylation eukaryotic initiation factor 2 alpha (eIF2α). Here we report identification a direct kinase eIF2α, microtubule affinity-regulating (MARK2), which phosphorylates eIF2α in response to proteotoxic stress. activity MARK2 was confirmed cells lacking 4 previously known kinases. itself found be substrate C delta (PKCδ), serves as sensor misfolding through dynamic interaction with heat shock 90 (HSP90). Both PKCδ are activated via proteotoxicity-associated neurodegenerative mouse models patients amyotrophic lateral sclerosis (ALS). These results reveal PKCδ-MARK2-eIF2α cascade that may play role responses