Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status.

Jiayu Chen, Xiping Liu, Fenglin Lü, Xinping Liu, Yi Ru, Yonggang Ren, Libo Yao, Yiguo Zhang

Index: FEBS Lett. 589 , 2347-58, (2015)

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Abstract

O-Linked N-acetylglucosamine transferase (OGT) was identified as an Nrf1-interacting protein. Herein, we show that Nrf1 enables interaction with OGT and their co-immunoprecipitates are O-GlcNAcylated by the enzyme. The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression. The turnover of Nrf1 is enhanced upon overexpression of OGT, which promotes ubiquitination of the CNC-bZIP protein. Furthermore, the serine/theorine-rich sequence of PEST2 degron within Nrf1 is identified to be involved in the protein O-GlcNAcylation by OGT. Overall, Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.