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.