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Exposure to metals induces numr-1 and numr-2 transcription in pharyngeal and intestinal cells. Other environmental stressors do not affect transcription, indicating that these are metal-specific, stress-responsive genes. NUMR-1 and NUMR-2 target to nuclei and colocalize with HSF-1, suggesting that they may be components of nuclear stress granules. Nematodes overexpressing NUMR-1 and NUMR-2 are resistant to stress and live longer than control animals; likewise reducing expression increases sensitivity to metals and decreases neuromuscular functions. Upstream regulatory regions of both genes contain potential binding sites for DAF-16 and SKN-1, which are components of the insulin-IGF-like signaling pathway. This pathway regulates longevity and stress responses in C. elegans. NUMR-1 and NUMR-2 may function to promote resistance to environmental stressors and longevity, which is mediated by the insulin-IGF-like signaling pathway.<\/jats:p>","DOI":"10.1242\/jcs.065433","type":"journal-article","created":{"date-parts":[[2010,5,26]],"date-time":"2010-05-26T01:44:40Z","timestamp":1274838280000},"page":"2124-2134","source":"Crossref","is-referenced-by-count":33,"title":["Molecular characterization of<i>numr-1<\/i>and<i>numr-2<\/i>: genes that increase both resistance to metal-induced stress and lifespan in<i>Caenorhabditis elegans<\/i>"],"prefix":"10.1242","volume":"123","author":[{"given":"Brooke E.","family":"Tvermoes","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, MD E1-05, PO Box 12233, 111 T. W. 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