RT Journal Article
T1 TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.
A1 McCallum, Katie C
A1 Liu, Bin
A1 Fierro-González, Juan Carlos
A1 Swoboda, Peter
A1 Arur, Swathi
A1 Miranda-Vizuete, Antonio
A1 Garsin, Danielle A
K1 ASJ neurons
K1 Caenorhabditis elegans
K1 cell non-autonomous signaling
K1 oxidative stress response
K1 thioredoxin
AB 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.
YR 2016
FD 2016-02-26
LK http://hdl.handle.net/10668/9874
UL http://hdl.handle.net/10668/9874
LA en
DS RISalud
RD Apr 11, 2025