SMK-1, an essential regulator of DAF-16-mediated longevity

Cell. 2006 Mar 10;124(5):1039-53. doi: 10.1016/j.cell.2005.12.042.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Forkhead Transcription Factors
  • 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
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • daf-16 protein, C elegans
  • Insulin-Like Growth Factor I