Transcription factor Nrf1 is negatively regulated by its O‐GlcNAcylation status. Issue 18 (29th July 2015)

• Record Type: Journal Article
• Authors: Chen, Jiayu; Liu, Xiping; Lü, Fenglin; Liu, Xinping; Ru, Yi; Ren, Yonggang; Yao, Libo; Zhang, Yiguo
• Is Part Of: FEBS letters. Volume 589:Issue 18(2015)
• Page Start: 2347
• Page End: 2358
• Publication Date: 2015-07-29
• Subjects: AD1 -- acidic domain 1 -- ARE -- antioxidant response element -- bZIP -- basic region-leucine zipper -- CHX -- cycloheximide -- CNC -- cap'n'collar -- EGFP -- enhanced green fluorescent protein -- ER -- endoplasmic reticulum -- Glc -- glucose -- GCLM -- glutamate cysteine ligase modifier subunit -- GlcNAc -- β-d-N-acetylglucosamine -- GlcNH2 -- glucosamine -- GST -- glutathione S-transferase -- HCF1 -- host cell factor 1 -- IP -- immunoprecipitation -- IB -- immunoblotting -- Nrf1 -- nuclear factor erythroid 2-related factor -- NST -- Asn/Ser/Thr-rich region -- OGT -- O-linked N-acetylglucosamine transferase -- OGA -- O-GlcNAcase -- PEST2 -- proline-glutamate-serine-threonine-rich sequence 2 -- siOGT -- siRNA targeting against OGT -- siNC -- a scrambled siRNA as a negative control -- TCF11 -- transcription factor 11 -- Ub -- ubiquitin -- Nuclear factor erythroid 2-related factor (Nrf1) -- O-GlcNAcylation -- O-Linked N-acetylglucosamine transferase (OGT) -- Transcriptional regulation -- Post-translational modification; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.07.030
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : 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.