Authors: 
H. Ma, S. Wolff, D. Burch, G. Maciel, P.J. Woodring, T. Hunter, A. Dillin
Category: 
Oral
Conference: 
Abstract: 

Insulin/IGF-1 signaling (IIS) regulates the aging process in worms, flies and mice. In the nematode Caenorhabditis elegans, IIS regulates processes in addition to aging such as early developmental decisions and the reproductive status of the animal. We present evidence for the placement of the uncharacterized gene, smk-1, within the insulin/IGF-1 pathway. Genetic analysis indicates that loss of smk-1 specifically influences the aging related function of the DAF-2 (IIS) signaling pathway. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus, transcriptional assays indicate that SMK-1 is required for maximal DAF-16/FOXO3a transcription, and physiological evidence suggests that DAF-16 and SMK-1 are capable of functional interaction in the nuclei of intestinal cells and neurons. Taken together, our data indicate that SMK-1 is a new component of the IIS longevity pathway, and the first that plays a role in longevity without affecting other processes regulated by IIS, presumably by modulating DAF-16 transcriptional specificity.

Keywords (Optional): 
insulin/IGF-1
C. elegans
longevity
FOXO3a
DAF-16