Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2047457 | FEBS Letters | 2015 | 12 Pages |
•Interaction of O-linked N-acetylglucosamine transferase (OGT) with Nrf1 is found.•The transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status.•Knockdown of OGT causes increases in the expression of Nrf1 and its target genes.•Over-expression of OGT enhanced turnover of Nrf1 through putative ubiquitination.•The PEST2 degron within Nrf1 is required for the protein O-GlcNAcylation by OGT.
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.