NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans

Mi Cheong Cheong, Hyoung Joo Lee, Keun Na, Hyoe Jin Joo, Leon Avery, Young Jai You, Young Ki Paik

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Nematode sterol-binding protein 1 (NSBP-1) is a homolog of nucleosome assembly protein 1 in mammals that is expressed widely in Caenorhabditis elegans. NSBP-1 mutants are biologically lethal, demonstrating the significance of the gene in growth and development. We investigated how cholesterol influences the insulin signaling pathway through this novel sterol-binding protein in C. elegans. Here we report that NSBP-1 influences many biological processes mediated by insulin signaling, such as longevity, dauer formation, fat storage, and resistance to oxidative stress. We found that NSBP-1 is phosphorylated by AKT-1 downstream of insulin signaling. In the absence of insulin signaling, NSBP-1 is translocated to the nucleus and binds to DAF-16, a FOXO transcription factor, in a cholesterol-dependent manner. Moreover, NSBP-1 and DAF-16 regulate a common set of genes that can directly modulate fat storage, longevity, and resistance to stress. Together, our results present a new steroid-binding molecule that can connect sterol signaling to insulin signaling through direct interaction with FOXO.

Original languageEnglish (US)
Pages (from-to)1623-1636
Number of pages14
JournalCellular and Molecular Life Sciences
Volume70
Issue number9
DOIs
StatePublished - May 2013

Keywords

  • C. elegans
  • Cholesterol
  • Cholesterol-binding protein
  • D2096.8
  • DAF-16
  • Insulin/IGF-1 signaling

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Fingerprint Dive into the research topics of 'NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans'. Together they form a unique fingerprint.

  • Cite this