| Title: | The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans |
| Author(s): | Ogg S; Paradis S; Gottlieb S; Patterson GI; Lee L; Tissenbaum HA; Ruvkun G; |
| Address: | "Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA" |
| ISSN/ISBN: | 0028-0836 (Print) 0028-0836 (Linking) |
| 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" |
| Keywords: | Alternative Splicing Amino Acid Sequence Animals Blood Proteins/chemistry Caenorhabditis elegans/genetics/*metabolism *Caenorhabditis elegans Proteins Cell Cycle Proteins DNA-Binding Proteins/chemistry Forkhead Box Protein O1 Forkhead Transcription Factor; |
| Notes: | "MedlineOgg, S Paradis, S Gottlieb, S Patterson, G I Lee, L Tissenbaum, H A Ruvkun, G eng Research Support, U.S. Gov't, P.H.S. England 1997/11/14 Nature. 1997 Oct 30; 389(6654):994-9. doi: 10.1038/40194" |
