title: Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity.
abstract: In the nematode Caenorhabditis elegans, inactivating mutations in the insulin/IGF-1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a FOXO-family transcription factor. Downstream protein activities that directly regulate longevity during impaired insulin/IGF-1 signaling (IIS) are poorly characterized. Here, we use global cysteine-reactivity profiling to identify protein activity changes during impaired IIS. Upon confirming that cysteine reactivity is a good predictor of functionality in C. elegans, we profiled cysteine-reactivity changes between daf-2 and daf-16;daf-2 mutants, and identified 40 proteins that display a >2-fold change. Subsequent RNAi-mediated knockdown studies revealed that lbp-3 and K02D7.1 knockdown caused significant increases in lifespan and dauer formation. The proteins encoded by these two genes, LBP-3 and K02D7.1, are implicated in intracellular fatty acid transport and purine metabolism, respectively. These studies demonstrate that cysteine-reactivity profiling can be complementary to abundance-based transcriptomic and proteomic studies, serving to identify uncharacterized mediators of C. elegans longevity.
authors: Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA.
authors: Julianne
authors: J
authors: Martell
authors: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Yonghak
authors: Y
authors: Seo
authors: Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA.
authors: Daniel W
authors: DW
authors: Bak
authors: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Samuel F
authors: SF
authors: Kingsley
authors: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Heidi A
authors: HA
authors: Tissenbaum
authors: Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA. Electronic address: eranthie@bc.edu.
authors: Eranthie
authors: E
authors: Weerapana
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D015398:Signal Transduction
chemical_list: D007334:Insulin-Like Growth Factor I; D003545:Cysteine