The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-10

AUTHORS

Scott Ogg, Suzanne Paradis, Shoshanna Gottlieb, Garth I. Patterson, Linda Lee, Heidi A. Tissenbaum, Gary Ruvkun

ABSTRACT

In mammals, insulin signalling regulates glucose transport together with the expression and activity of various metabolic enzymes. In the nematode Caenorhabditis elegans, a related pathway regulates metabolism, development and longevity. Wild-type animals enter the developmentally arrested dauer stage in response to high levels of a secreted pheromone, accumulating large amounts of fat in their intestines and hypodermis. Mutants in DAF-2 (a homologue of the mammalian insulin receptor) and AGE-1 (a homologue of the catalytic subunit of mammalian phosphatidylinositol 3-OH kinase) arrest development at the dauer stage. Moreover, animals bearing weak or temperature-sensitive mutations in daf-2 and age-1 can develop reproductively, but nevertheless show increased energy storage and longevity. Here we show that null mutations in daf-16 suppress the effects of mutations in daf-2 or age-1; lack of daf-16 bypasses the need for this insulin receptor-like signalling pathway. The principal role of DAF-2/AGE-1 signalling is thus to antagonize DAF-16. daf-16 is widely expressed and encodes three members of the Fork head family of transcription factors. The DAF-2 pathway acts synergistically with the pathway activated by a nematode TGF-beta-type signal, DAF-7, suggesting that DAF-16 cooperates with nematode SMAD proteins in regulating the transcription of key metabolic and developmental control genes. The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. These genes may be dysregulated in diabetes. More... »

PAGES

994-999

Journal

TITLE

Nature

ISSUE

6654

VOLUME

389

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/40194

DOI

http://dx.doi.org/10.1038/40194

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022762380

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9353126


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