title: Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status.
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.
authors.affiliation: Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China; Department of Biochemistry and Molecular Biology, Zunyi Medical College, Zunyi 563000, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Zunyi Medical College, Zunyi 563000, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Lü
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ru
authors.affiliation: Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.affiliation: Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China. Electronic address: yiguozhang@cqu.edu.cn.
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D000975:Antioxidants; D051265:NF-E2-Related Factor 1; C088357:NFE2L1 protein, human; D012097:Repressor Proteins; D017351:N-Acetylglucosaminyltransferases; C037649:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine
keywords: Nuclear factor erythroid 2-related factor (Nrf1); O-GlcNAcylation; O-Linked N-acetylglucosamine transferase (OGT); Post-translational modification; Transcriptional regulation