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A new DAF-16 isoform regulates longevity.
Nature. 2010 Jul 22; 466(7305):498-502.Nat

Abstract

The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway. One of two isoforms, DAF-16a, is known to regulate longevity, stress response and dauer diapause. However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate IIS-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases, and regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions, and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the IIS-mediated processes in the context of a whole organism.

Authors+Show Affiliations

Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.No 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

20613724

Citation

Kwon, Eun-Soo, et al. "A New DAF-16 Isoform Regulates Longevity." Nature, vol. 466, no. 7305, 2010, pp. 498-502.
Kwon ES, Narasimhan SD, Yen K, et al. A new DAF-16 isoform regulates longevity. Nature. 2010;466(7305):498-502.
Kwon, E. S., Narasimhan, S. D., Yen, K., & Tissenbaum, H. A. (2010). A new DAF-16 isoform regulates longevity. Nature, 466(7305), 498-502. https://doi.org/10.1038/nature09184
Kwon ES, et al. A New DAF-16 Isoform Regulates Longevity. Nature. 2010 Jul 22;466(7305):498-502. PubMed PMID: 20613724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new DAF-16 isoform regulates longevity. AU - Kwon,Eun-Soo, AU - Narasimhan,Sri Devi, AU - Yen,Kelvin, AU - Tissenbaum,Heidi A, Y1 - 2010/07/07/ PY - 2010/01/07/received PY - 2010/05/14/accepted PY - 2010/7/9/entrez PY - 2010/7/9/pubmed PY - 2010/9/10/medline SP - 498 EP - 502 JF - Nature JO - Nature VL - 466 IS - 7305 N2 - The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway. One of two isoforms, DAF-16a, is known to regulate longevity, stress response and dauer diapause. However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate IIS-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases, and regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions, and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the IIS-mediated processes in the context of a whole organism. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/20613724/A_new_DAF_16_isoform_regulates_longevity_ L2 - https://doi.org/10.1038/nature09184 DB - PRIME DP - Unbound Medicine ER -