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Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans

dc.contributor.author Tvermoes, Brooke E
dc.contributor.author Boyd, Windy A
dc.contributor.author Freedman, Jonathan H
dc.date.accessioned 2011-06-21T17:27:35Z
dc.date.available 2011-06-21T17:27:35Z
dc.date.issued 2010
dc.identifier.citation Tvermoes,Brooke E.;Boyd,Windy A.;Freedman,Jonathan H.. 2010. Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans. Journal of cell science 123(12): 2123-2133.
dc.identifier.issn 0021-9533
dc.identifier.uri https://hdl.handle.net/10161/4187
dc.description.abstract To define the mechanisms involved in the molecular response to the carcinogenic metal cadmium, two novel metal-inducible genes from C. elegans were characterized: numr-1 and numr-2 (nuclear localized metal responsive). numr-1 and numr-2 sequences and cellular patterns of expression are identical, indicating that these are functionally equivalent genes. Constitutive transcription of numr-1 and numr-2 is developmentally regulated and occurs in the intestine, in head and tail neurons, and vulva muscles. 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.
dc.language.iso en_US
dc.publisher The Company of Biologists
dc.relation.isversionof 10.1242/jcs.065433
dc.subject c. elegans
dc.subject cadmium
dc.subject stress response
dc.subject lifespan
dc.subject longevity
dc.subject shock transcription factor-1
dc.subject unfolded protein response
dc.subject cell-specific
dc.subject expression
dc.subject c-elegans
dc.subject cadmium toxicity
dc.subject oxidative stress
dc.subject heavy-metal
dc.subject metallothionein genes
dc.subject regulatory elements
dc.subject signaling pathways
dc.subject cell biology
dc.title Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans
dc.title.alternative
dc.type Other article
dc.description.version Version of Record
duke.date.pubdate 2010-6-15
duke.description.issue 12
duke.description.volume 123
dc.relation.journal Journal of cell science
pubs.begin-page 2123
pubs.end-page 2133


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