TY - JOUR
T1 - TRX-1 regulates SKN-1 nuclear localization cell non-autonomously in caenorhabditis elegans
AU - McCallum, Katie C.
AU - Liu, Bin
AU - Fierro-González, Juan Carlos
AU - Swoboda, Peter
AU - Arur, Swathi
AU - Miranda-Vizuete, Antonio
AU - Garsin, Danielle A.
N1 - Publisher Copyright:
© 2016 by the Genetics Society of America.
PY - 2016/5
Y1 - 2016/5
N2 - 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.
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.
KW - ASJ neurons
KW - Caenorhabditis elegans
KW - Cell non-autonomous signaling
KW - Oxidative stress response
KW - Thioredoxin
UR - http://www.scopus.com/inward/record.url?scp=84979903024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979903024&partnerID=8YFLogxK
U2 - 10.1534/genetics.115.185272
DO - 10.1534/genetics.115.185272
M3 - Article
C2 - 26920757
AN - SCOPUS:84979903024
SN - 0016-6731
VL - 203
SP - 387
EP - 402
JO - Genetics
JF - Genetics
IS - 1
ER -