SLR-2 and JMJC-1 regulate an evolutionarily conserved stress-response network.
Maintaining a homeostatic interaction with the environment is crucial for the growth, survival, and propagation of all living organisms. Reestablishment of equilibrium after stress is achieved by the activation of complex transcriptional-response networks, many of which remain poorly understood. Here, we report that the zinc-finger protein, SLR-2, is a master stress regulator and is required for the normal response to pleiotropic stress conditions in Caenorhabditis elegans. Using bioinformatical tools, we identified an evolutionarily conserved nucleotide motif present in slr-2 stress-responsive genes and show that this motif is sufficient for stress induction under a variety of conditions. We also demonstrate that JMJC-1, a conserved Jumonji C domain protein, acts downstream of SLR-2 to mediate stress response in C. elegans. Moreover, the role of JMJC-1 in stress response is conserved in Drosophila and mammals. Finally, we provide evidence that the SLR-2-JMJC-1 pathway functions independently of the well-studied DAF-16/FOXO1 network. These findings point to a previously unrecognized phylogenetically conserved master stress-response pathway in metazoa.
Kirienko
Natalia V
NV
Department of Molecular Biology, College of Agriculture, University of Wyoming, Laramie, WY 82071, USA.
Fay
David S
DS
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018509:DNA, Helminth / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008322:Mammals; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D056484:Jumonji Domain-Containing Histone Demethylases