title: O-GlcNAcylation of SKN-1 modulates the lifespan and oxidative stress resistance in Caenorhabditis elegans.
abstract: In C. elegans, the transcription factor skinhead-1 (SKN-1), the ortholog of human NF-E2-related factor 2 (Nrf-2), plays important roles in oxidative stress defense and aging processes. It has been documented that the activity of SKN-1 is regulated by its phosphorylation modification. However, whether other posttranslational modifications of SKN-1 affect its function remains unclear to date. Here we report, for the first time, that SKN-1 is O-GlcNAcylated at Ser470 and Thr493 by O-GlcNActransferase OGT-1. By generating the double mutations of Ser470/Thr493 in the wild type and skn-1(zu67) worms, respectively, we found that disruption of O-GlcNAc modification on SKN-1 repressed the accumulation of SKN-1 in the intestinal nuclei, and decreased the activities of SKN-1 in modulating lifespan and oxidative stress resistance. Moreover, under oxidative stress, SKN-1 was highly O-GlcNAcylated, resulting in the decrease of GSK-3-mediated phosphorylation at Ser483 adjacent to the O-GlcNAcylated residues (Ser470 and Thr493). These data suggest that O-GlcNAcylation of SKN-1 is crucial for regulating lifespan and oxidative stress resistance via the crosstalk with its phosphorylation in C. elegans. These findings have important implications for studying the functions of O-GlcNAcylation on Nrf-2 in human aging-related diseases.
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: 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: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Liangping
authors.initials: L
authors.lastname: Su
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Lin
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
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.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
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
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006031:Glycosylation; D008136:Longevity; D008954:Models, Biological; D009154:Mutation; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans