title: NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans.
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.
authors.affiliation: Department of Biochemistry and Integrated Omics for Biomedical Science (WCU Program), College of Life Science and Biotechnology and Yonsei Proteome Research Center, Yonsei University, 134 Shinchon-dong, Sudaemoon-ku, Seoul 120-749, Korea.
authors.forename: Mi Cheong
authors.initials: MC
authors.lastname: Cheong
authors.forename: Hyoung-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Keun
authors.initials: K
authors.lastname: Na
authors.forename: Hyoe-Jin
authors.initials: HJ
authors.lastname: Joo
authors.forename: Leon
authors.initials: L
authors.lastname: Avery
authors.forename: Young-Jai
authors.initials: YJ
authors.lastname: You
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol