Glycosylation of KEAP1 links nutrient sensing to redox stress signaling.

ABSTRACT: O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets. Guided by this information, we identified KEAP1 (also known as KLHL19), the primary negative regulator of NRF2, as a direct substrate of OGT We show that O-GlcNAcylation of KEAP1 at serine 104 is required for the efficien

SUBMITTER: Chen PH 

PROVIDER: S-EPMC5538768 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature