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Gene Review

daf-12  -  Protein DAF-12

Caenorhabditis elegans

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Disease relevance of daf-12

  • We find that loss-of-function mutations in any of three genes (daf-16, daf-18, or daf-12) not only reduce or abolish the ability to form dauers but also block the hormetic response increasing life span following sub-lethal heat stress [1].

High impact information on daf-12

  • We have also identified a potential daf-12-response element within lin-28 3'UTR and show that two microRNA (miRNA) (lin-4 and let-7)-binding sites mediate redundant inhibitory activities that are likely lin-66-independent [2].
  • Genetic tests show that daf-9 is upstream of daf-12 in the genetic pathways for larval development and adult longevity. daf-9 encodes a cytochrome P450 related to those involved in biosynthesis of steroid hormones in mammals [3].
  • In these mutants, somatic cells repeat L2-specific cellular programs of division and migration at the L3 stage; epistasis experiments place daf-12 between lin-14 and lin-28 within the heterochronic pathway [4].
  • We provide evidence that lin-14 inhibits a negative regulation that is independent of the lin-4 RNA and involves the gene daf-12, which encodes a nuclear hormone receptor [5].
  • Three complementation groups correspond to the previously described genes daf-3, daf-5, and daf-12 [6].

Biological context of daf-12

  • Two parallel chemosensory signal transduction pathways, one of which is transforming growth factor (TGF)-beta-like, converge on the daf-12 gene to regulate dauer formation [7].

Anatomical context of daf-12

  • The daf-12 promoter directs expression of GFP in the pharynx. daf-12 is a C. elegans nuclear hormone receptor with multiple isoforms, is expressed throughout development in distinct cells, and functions under a variety of environmental conditions [7].

Associations of daf-12 with chemical compounds


Regulatory relationships of daf-12

  • The increased life span caused by the daf-2 mutation can be enhanced by a daf-12 mutation and suppressed by a daf-16 mutation [9].

Other interactions of daf-12

  • Mutations in three genes (daf-16, daf-18, and daf-12) block hormetically induced life extension [10].
  • Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner [11].
  • PREG extends the lifespan of germline-defective daf-9 mutants dramatically, but has no effect on daf-12 mutants [12].
  • LPP and PTK activities decreased similarly in daf-12(m20), and a control strain that had wild-type alleles of daf-12, age-1, and daf-2 [13].
  • We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells, while the forkhead transcription factor pha-4 is a target in the intestine [14].


  1. Hormesis in Caenorhabditis elegans dauer-defective mutants. Cypser, J.R., Johnson, T.E. Biogerontology. (2003) [Pubmed]
  2. Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans. Morita, K., Han, M. EMBO J. (2006) [Pubmed]
  3. DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity. Jia, K., Albert, P.S., Riddle, D.L. Development (2002) [Pubmed]
  4. daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Antebi, A., Culotti, J.G., Hedgecock, E.M. Development (1998) [Pubmed]
  5. Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Seggerson, K., Tang, L., Moss, E.G. Dev. Biol. (2002) [Pubmed]
  6. Suppressors of transforming growth factor-beta pathway mutants in the Caenorhabditis elegans dauer formation pathway. Inoue, T., Thomas, J.H. Genetics (2000) [Pubmed]
  7. Structure and expression of daf-12: a nuclear hormone receptor with three isoforms that are involved in development and aging in Caenorhabditis elegans. Snow, M.I., Larsen, P.L. Biochim. Biophys. Acta (2000) [Pubmed]
  8. A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Gerisch, B., Weitzel, C., Kober-Eisermann, C., Rottiers, V., Antebi, A. Dev. Cell (2001) [Pubmed]
  9. Protein carbonyl accumulation in aging dauer formation-defective (daf) mutants of Caenorhabditis elegans. Yasuda, K., Adachi, H., Fujiwara, Y., Ishii, N. J. Gerontol. A Biol. Sci. Med. Sci. (1999) [Pubmed]
  10. Hormesis and aging in Caenorhabditis elegans. Cypser, J.R., Tedesco, P., Johnson, T.E. Exp. Gerontol. (2006) [Pubmed]
  11. Genes that regulate both development and longevity in Caenorhabditis elegans. Larsen, P.L., Albert, P.S., Riddle, D.L. Genetics (1995) [Pubmed]
  12. A steroid hormone that extends the lifespan of Caenorhabditis elegans. Broué, F., Liere, P., Kenyon, C., Baulieu, E.E. Aging Cell (2007) [Pubmed]
  13. Age-specific modulation of light production potential, and alkaline phosphatase and protein tyrosine kinase activities in various age mutants of Caenorhabditis elegans. Vanfleteren, J.R., Braeckman, B.P., Roelens, I., De Vreese, A. J. Gerontol. A Biol. Sci. Med. Sci. (1998) [Pubmed]
  14. The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans. Grosshans, H., Johnson, T., Reinert, K.L., Gerstein, M., Slack, F.J. Dev. Cell (2005) [Pubmed]
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