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Gene Review:

daf-18 - Protein DAF-18

Caenorhabditis elegans

Suzuki, Y. et al., Rouault, J.P. et al., Gil, E.B. et al., Ahmed, S., Cypser, J.R. et al., et al.

Cypser, Johnson, Ahmed, Cypser, Tedesco, Johnson,

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Disease relevance of daf-18

Given the conservation of the PI3'K signaling pathway between C. elegans and mammals, the analysis of daf-18 PTEN mutant nematodes should shed light on the role of human PTEN in the etiology of metabolic disease, aging, and cancer [1].

High impact information on daf-18

We provide evidence that daf-18 elicits some functions independent of the downstream gene daf-16 [2].
In one example, daf-18 appears to constitute a cell-autonomous germline signal that converges with a somatic gonad signal mediated by ceh-18 at a kinase inhibition [2].
We show that at least 27 genes collaborate with the worm PTEN homolog daf-18 for various functions previously concealed by genetic redundancy, including embryogenesis, cuticle turnover, egg laying, and oocyte maturation [2].
Others have shown that mutation of daf-18 suppresses the life extension and constitutive dauer formation associated with daf-2 or age-1 mutants [3].
Similarly, we show that inactivation of daf-18 by RNA-mediated interference mimics this suppression, and that a wild-type daf-18 transgene rescues the dauer defect [3].

Biological context of daf-18

These theories were tested in the nematode Caenorhabditis elegans by examining the consequences of eliminating either apoptosis or the daf-16, daf-18 or sir-2.1 genes that promote longevity of postmitotic somatic cells [4].

Other interactions of daf-18

Mutations in three genes (daf-16, daf-18, and daf-12) block hormetically induced life extension [5].
Additionally, we find that daf-16 and daf-12 are not required for the induction of thermotolerance, but daf-18 is required for its full induction [6].

References

Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene. Gil, E.B., Malone Link, E., Liu, L.X., Johnson, C.D., Lees, J.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
Genetic redundancy masks diverse functions of the tumor suppressor gene PTEN during C. elegans development. Suzuki, Y., Han, M. Genes Dev. (2006) [Pubmed]
Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Rouault, J.P., Kuwabara, P.E., Sinilnikova, O.M., Duret, L., Thierry-Mieg, D., Billaud, M. Curr. Biol. (1999) [Pubmed]
Uncoupling of pathways that promote postmitotic life span and apoptosis from replicative immortality of Caenorhabditis elegans germ cells. Ahmed, S. Aging Cell (2006) [Pubmed]
Hormesis and aging in Caenorhabditis elegans. Cypser, J.R., Tedesco, P., Johnson, T.E. Exp. Gerontol. (2006) [Pubmed]
Hormesis in Caenorhabditis elegans dauer-defective mutants. Cypser, J.R., Johnson, T.E. Biogerontology. (2003) [Pubmed]

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