Elucidating the redox-proteolysis switch for transcriptional induction of the ubiquitin proteasome system (UPS) in space and time (A13)

蛋白毒性应激伴随着活性氧（ROS）的产生和ER应激的诱导。一个转录反馈环调节UPS依赖的蛋白降解反应蛋白毒性和氧化应激通过激活的ER-拴转录因子TCF 11。TCF 11的膜释放和核转位由包含ROS的分子开关和近膜蛋白水解裂解触发。该项目旨在阐明这种开关控制细胞反应，以利用先进的细胞生物学，化学和遗传工具在细胞培养和C.优雅

Proteotoxic stress is accompanied by the production of reactive oxygen species (ROS) and by induction of ER stress. A transcriptional feed-back-loop regulates UPS-dependent protein degradation in response to proteotoxic and oxidative stress via activation of the ER-tethered transcription factor TCF11. The membrane release and nuclear translocation of TCF11 is triggered by a molecular switch comprising ROS and a juxta-membrane proteolytic cleavage. The project aims to elucidate this switch controlling cellular responses to rebalance redox and protein homeostasis with spatial and temporal resolution using advanced cell biology, chemical and genetic tools in cell culture and C. elegans.