TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans
| Autor: | Katie C. McCallum, Swathi Arur, Juan Carlos Fierro-González, Bin Liu, Peter Swoboda, Antonio Miranda-Vizuete, Danielle A. Garsin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal structures Cell Active Transport Cell Nucleus Investigations p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Thioredoxins 0302 clinical medicine Genetics medicine Animals Intestinal Mucosa Caenorhabditis elegans Proteins Thioredoxin Caenorhabditis elegans Gene Transcription factor ASJ neurons Cell Nucleus Neurons biology Oxidative stress response biology.organism_classification Cell biology DNA-Binding Proteins Intestines Oxidative Stress Cell nucleus 030104 developmental biology medicine.anatomical_structure Cell non-autonomous signaling Signal transduction 030217 neurology & neurosurgery Nuclear localization sequence Signal Transduction Transcription Factors |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1943-2631 0016-6731 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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