Tags

Type your tag names separated by a space and hit enter

The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO.
PLoS Genet. 2011 Sep; 7(9):e1002235.PG

Abstract

The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Authors+Show Affiliations

Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.No affiliation info availableNo affiliation info availableNo 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

21909281

Citation

Rizki, Gizem, et al. "The Evolutionarily Conserved Longevity Determinants HCF-1 and SIR-2.1/SIRT1 Collaborate to Regulate DAF-16/FOXO." PLoS Genetics, vol. 7, no. 9, 2011, pp. e1002235.
Rizki G, Iwata TN, Li J, et al. The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 2011;7(9):e1002235.
Rizki, G., Iwata, T. N., Li, J., Riedel, C. G., Picard, C. L., Jan, M., Murphy, C. T., & Lee, S. S. (2011). The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genetics, 7(9), e1002235. https://doi.org/10.1371/journal.pgen.1002235
Rizki G, et al. The Evolutionarily Conserved Longevity Determinants HCF-1 and SIR-2.1/SIRT1 Collaborate to Regulate DAF-16/FOXO. PLoS Genet. 2011;7(9):e1002235. PubMed PMID: 21909281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. AU - Rizki,Gizem, AU - Iwata,Terri Naoko, AU - Li,Ji, AU - Riedel,Christian G, AU - Picard,Colette Lafontaine, AU - Jan,Max, AU - Murphy,Coleen T, AU - Lee,Siu Sylvia, Y1 - 2011/09/01/ PY - 2011/01/27/received PY - 2011/06/28/accepted PY - 2011/9/13/entrez PY - 2011/9/13/pubmed PY - 2012/1/10/medline SP - e1002235 EP - e1002235 JF - PLoS genetics JO - PLoS Genet. VL - 7 IS - 9 N2 - The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/21909281/The_evolutionarily_conserved_longevity_determinants_HCF_1_and_SIR_2_1/SIRT1_collaborate_to_regulate_DAF_16/FOXO_ L2 - http://dx.plos.org/10.1371/journal.pgen.1002235 DB - PRIME DP - Unbound Medicine ER -