RRC ID 59410
Author Son HG, Seo K, Seo M, Park S, Ham S, An SWA, Choi ES, Lee Y, Baek H, Kim E, Ryu Y, Ha CM, Hsu AL, Roh TY, Jang SK, Lee SV.
Title Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans.
Journal Genes Dev
Abstract Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.
Volume 32(23-24)
Pages 1562-1575
Published 2018-12-1
DOI 10.1101/gad.317362.118
PII gad.317362.118
PMID 30478249
PMC PMC6295163
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Forkhead Transcription Factors / metabolism* Insulin / metabolism Insulin-Like Growth Factor I / metabolism Intestines / physiology Longevity / genetics* Molecular Chaperones / genetics Molecular Chaperones / metabolism* Protein Binding Signal Transduction / genetics Subcutaneous Tissue / physiology Transcription Factors / metabolism* Transcriptional Activation / genetics
IF 8.99
Times Cited 5
C.elegans tm1714 tm3759 tm3510