title: Methylation of arginine by PRMT1 regulates Nrf2 transcriptional activity during the antioxidative response.
abstract: The cap 'n' collar (CNC) family of transcription factors play important roles in resistance of oxidative and electrophilic stresses. Among the CNC family members, NF-E2-related factor 2 (Nrf2) is critical for regulating the antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. The activity of Nrf2 is controlled by a variety of post-translational modifications, including phosphorylation, ubiquitination, acetylation and sumoylation. Here we demonstrate that the arginine methyltransferase-1 (PRMT1) methylates Nrf2 protein at a single residue of arginine 437, both in vitro and in vivo. Using the heme oxygenase-1 (HO-1) as a model of phase II enzyme gene, we found that methylation of Nrf2 by PRMT1 led to a moderate increase of its DNA-binding activity and transactivation, which subsequently protected cells against the tBHP-induced glutathione depletion and cell death. Collectively, our results define a novel modification of Nrf2, which operates as a fine-tuning mechanism for the transcriptional activity of Nrf2 under the oxidative stress.
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Geng
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Li
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. Electronic address: zhangy288@nenu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China. Electronic address: luj809@nenu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D061745:Antioxidant Response Elements; D001120:Arginine / Q000378:metabolism; D015687:Cell Hypoxia; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter; D057809:HEK293 Cells; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D056945:Hep G2 Cells; D042421:Histone Code; D006801:Humans; D008745:Methylation; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010545:Peroxides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010545:Peroxides; D011994:Recombinant Proteins; D012097:Repressor Proteins; D004247:DNA; D001120:Arginine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D050880:p300-CBP Transcription Factors; C000602361:tert-butyl peroxide
keywords: HO-1; Methylation of arginine; Nrf2; Oxidative stress; PRMT1