Authors: Wolff S; Ma H; Burch D; Maciel GA; Hunter T; Dillin A
Abstract: Insulin/IGF-1 signaling (IIS) regulates aging in worms, flies, and mice through a well-characterized, highly conserved core set of components. IIS also regulates early developmental decisions, the reproductive status of the animal, innate immunity, and stress-resistance functions. In C. elegans, the sole insulin/IGF-1 receptor, DAF-2, negatively regulates the FOXO transcription factor, DAF-16. We report here on a new component of the IIS longevity pathway, SMK-1, which specifically influences DAF-16-dependent regulation of the aging process in C. elegans by regulating the transcriptional specificity of DAF-16 activity. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus. Physiological and transcription analyses indicate that smk-1 is required for the innate immune, UV, and oxidative stress but not the thermal stress functions of DAF-16. SMK-1 therefore plays a role in longevity by modulating DAF-16 transcriptional specificity without affecting other processes regulated by IIS.Keywords: Aging/physiology; Animals; Animals, Genetically Modified; Caenorhabditis elegans/cytology/*genetics/physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Cell Nucleus/metabolism; Gene Expression Regulation; Genes, Reporter; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; Longevity/*physiology; Models, Animal; RNA Interference; Signal Transduction/physiology; Transcription Factors/genetics/*metabolism; Transcription, Genetic
Date: March 15, 2006
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Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124: 1039-53.