daf-16;daf-2;wwp-1

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

E3 ubiquitin-protein ligase;WW domain Protein (E3 ubiquitin ligase)

Locus: CELE_Y65B4BR.4

Wormbase description: wwp-1 encodes, by alternative splicing, two isoforms of a putative E3 ubiquitin ligase orthologous to budding yeast Rsp5, Drosophila SU(DX), and human WWP1 (OMIM:602307) and WWP2 (OMIM:602308); WWP-1 is required for proteolysis of the intracellular LIN-12 domain in primary ventral precursor cells, and for protection of germ cells against ionizing radiation or camptothecin, as well as for normal acetylcholine neurotransmission, axonal guidance and fasciculation, patterning of the ventral nerve cord, locomotion, fat content, and late embryonic morphogenesis; in UV-irradiated nondauer larvae, WWP-1 stimulates the proteolysis of AMA-1; although WWP-1's is normally blocked from fully activating AMA-1 proteolysis by XPA-1/RAD-3, it also cooperates with XPA-1/RAD-3 to protect worms from UV-irradiation; WWP-1 is expressed in many neurons (cholinergic and GABAergic motor neurons, head, tail, body, and nerve cords), in larval and adult pharynx, intestine, renal gland cells and rectal epithelium, and in adult vulval muscle, body wall muscle, and coelomocytes; WWP-1 contains an N-terminal C2 domain, four central WW repeats and a C-terminal HECT ubiquitin ligase domain; WWP-1 binds UBC-18 in yeast two-hybrid assays, but is not required for UBC-18's activity in pharyngeal development.