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 longevity1,2. Wild-type animals enter the developmentally arrested dauer stage in response to high levels of a secreted pheromone3, 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 stage3. Moreover, animals bearing weak or temperature-sensitive mutations in daf-2 and age-1 can develop reproductively, but nevertheless show increased energy storage and longevity1,2,4,5. 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-β-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-β 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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59 bypass
60 control genes
61 cooperate
62 daf-2
63 daf-2/age
64 dauer stage
65 development
66 developmental control genes
67 diabetes
68 effect
69 effects of mutations
70 elegans
71 energy storage
72 enzyme
73 expression
74 factors
75 family
76 fat
77 fork head family
78 genes
79 glucose transport
80 head family
81 high levels
82 human orthologue
83 hypodermis
84 insulin
85 insulin signaling
86 intestine
87 lack
88 large amount
89 levels
90 longevity signals
91 mammals
92 members
93 metabolic enzymes
94 metabolic regulation
95 metabolism
96 mutants
97 mutations
98 need
99 nematode Caenorhabditis elegans
100 null mutation
101 orthologues
102 pathway
103 principal role
104 protein
105 regulation
106 related pathways
107 response
108 role
109 signaling
110 signals
111 stage
112 stage3
113 storage
114 suppresses
115 temperature-sensitive mutation
116 transcription
117 transcription factors
118 transduces
119 transport
120 wild-type animals
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