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

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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.