Inhibition of NGLY1 inactivates the transcription factor Nrf1 and potentiates proteasome inhibitor cytotoxicity
Year: 2017
Type: preprint
Abstract: We discovered that the proteostasis modulating transcription factor Nrf1 requires cytosolic de-N-glycosylation by the N-glycanase NGly1 as part of its activation mechanism. Through a covalent small molecule library screen, we discovered an inhibitor of NGly1 that blocks Nrf1 activation in cells and potentiates the activity of proteasome inhibitor cancer drugs. The requirement of NGly1 for Nrf1 activity likely underlies several pathologies associated with a rare hereditary deficiency in NGly1.
Source: ChemRxiv
Authors: Carolyn Bertozzi, Fred Tomlin, Ulla Gerling-Driessen, Yi-Chang Liu, Ryan Flynn, Janakiram Vangala, Christian Lentz, Sandra Clauder-Muenster, Petra Jakob, William F. Mueller, Diana Ordoñez-Rueda, Malte Paulsen, Naoko Matsui, Deirdre Foley, Agnes Rafalko, Tadashi Suzuki, Matthew Bogyo, Lars M. Steinmetz, Senthil K. Radhakrishnan
Institution: Stanford University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4250936706