Reference - Detail
RRC ID | 45949 |
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Author | Cheong MC, Lee HJ, Na K, Joo HJ, Avery L, You YJ, Paik YK. |
Title | NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans. |
Journal | Cell Mol Life Sci |
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. |
Volume | 70(9) |
Pages | 1623-36 |
Published | 2013-5-1 |
DOI | 10.1007/s00018-012-1221-0 |
PMID | 23255046 |
PMC | PMC3759162 |
MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / analysis Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / analysis Carrier Proteins / genetics Carrier Proteins / metabolism* Cholesterol / metabolism* Forkhead Transcription Factors Gene Expression Insulin / metabolism* Insulin-Like Growth Factor I / metabolism* Protein Binding Protein Transport Signal Transduction Transcription Factors / metabolism Transcriptional Activation Up-Regulation |
IF | 6.496 |
Times Cited | 10 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
Resource | |
C.elegans | tm1278 |