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

• Sterols may be the daf-9 substrate and daf-12 ligand because cholesterol deprivation phenocopies mutant defects [8].

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].

References