title: TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.
abstract: The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.
authors.affiliation: Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center, Houston, Texas 77030 The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030.
authors.forename: Katie C
authors.initials: KC
authors.lastname: McCallum
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 Center for Genetics and Genomics, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biosciences and Nutrition at Novum, Karolinska Institute, S-141 83 Huddinge, Sweden.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fierro-González
authors.affiliation: Department of Biosciences and Nutrition at Novum, Karolinska Institute, S-141 83 Huddinge, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
authors.affiliation: The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030 Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 Center for Genetics and Genomics, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Cientfícas/Universidad de Sevilla, E-41013 Sevilla, Spain danielle.a.garsin@uth.tmc.edu amiranda-ibis@us.es.
authors.forename: Antonio
authors.identifier: 0000-0002-6856-5396
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.affiliation: Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center, Houston, Texas 77030 The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030 danielle.a.garsin@uth.tmc.edu amiranda-ibis@us.es.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Garsin
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C508778:TRX-1 protein, C elegans; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D013879:Thioredoxins; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ASJ neurons; Caenorhabditis elegans; cell non-autonomous signaling; oxidative stress response; thioredoxin