RRC ID 36828
著者 McCallum KC, Liu B, Fierro-González JC, Swoboda P, Arur S, Miranda-Vizuete A, Garsin DA.
タイトル TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.
ジャーナル Genetics
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.
巻・号 203(1)
ページ 387-402
公開日 2016-5-1
DOI 10.1534/genetics.115.185272
PII genetics.115.185272
PMID 26920757
PMC PMC4858787
MeSH Active Transport, Cell Nucleus Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Intestinal Mucosa / metabolism Intestines / cytology Neurons / metabolism Oxidative Stress Signal Transduction* Thioredoxins / genetics Thioredoxins / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism
IF 4.015
引用数 10
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2720 tm2820