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Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator.
PLoS Biol. 2008 Sep 30; 6(9):e233.PB

Abstract

The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous nuclear localization and physically associated with DAF-16. Furthermore, loss of hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target genes and altered expression of a subset of DAF-16-regulated genes. We propose that HCF-1 modulates C. elegans longevity and stress response by forming a complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target gene promoters, and thereby regulates DAF-16-mediated transcription of selective target genes. As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals.

Authors+Show Affiliations

Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18828672

Citation

Li, Ji, et al. "Caenorhabditis Elegans HCF-1 Functions in Longevity Maintenance as a DAF-16 Regulator." PLoS Biology, vol. 6, no. 9, 2008, pp. e233.
Li J, Ebata A, Dong Y, et al. Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol. 2008;6(9):e233.
Li, J., Ebata, A., Dong, Y., Rizki, G., Iwata, T., & Lee, S. S. (2008). Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biology, 6(9), e233. https://doi.org/10.1371/journal.pbio.0060233
Li J, et al. Caenorhabditis Elegans HCF-1 Functions in Longevity Maintenance as a DAF-16 Regulator. PLoS Biol. 2008 Sep 30;6(9):e233. PubMed PMID: 18828672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. AU - Li,Ji, AU - Ebata,Atsushi, AU - Dong,Yuqing, AU - Rizki,Gizem, AU - Iwata,Terri, AU - Lee,Siu Sylvia, PY - 2008/06/23/received PY - 2008/08/15/accepted PY - 2008/10/3/pubmed PY - 2008/11/13/medline PY - 2008/10/3/entrez SP - e233 EP - e233 JF - PLoS biology JO - PLoS Biol. VL - 6 IS - 9 N2 - The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous nuclear localization and physically associated with DAF-16. Furthermore, loss of hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target genes and altered expression of a subset of DAF-16-regulated genes. We propose that HCF-1 modulates C. elegans longevity and stress response by forming a complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target gene promoters, and thereby regulates DAF-16-mediated transcription of selective target genes. As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals. SN - 1545-7885 UR - https://www.unboundmedicine.com/medline/citation/18828672/Caenorhabditis_elegans_HCF_1_functions_in_longevity_maintenance_as_a_DAF_16_regulator_ L2 - http://dx.plos.org/10.1371/journal.pbio.0060233 DB - PRIME DP - Unbound Medicine ER -