daf-2;mdt-15

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.

---

Mediator of RNA polymerase II transcription subunit 15

---

Locus: CELE_R12B2.5

---

Wormbase description: mdt-15 encodes, by alternative splicing, two isoforms of a Mediator subunit orthologous to human MED15; together with NHR-49 and SBP-1, MDT-15 is required for normal fat accumulation, for expression of fatty acid (FA) desaturase genes (fat-5, fat-6, and fat-7), for normal levels of mono- and polyunsaturated FAs (PUFAs), and for viability, fecundity, mobility, and normally long lifespan; several of these phenotypes can be at least partially suppressed by supplying PUFAs in the food medium; in part through NHR-49, MDT-15 participates in basal and fasting-induced transcription of numerous other metabolic genes, such as gei-7 and acs-2; independently of NHR-49 and SBP-1, MDT-15 ensures appropriate transcriptional response and survival in response to toxins and heavy metals by inducing select detoxification genes encoding such as cdr-1, cyp-35C1, gst-5, mtl-1, mtl-2, ugt-1, ugt-8, and others; mdt-15 is expressed at constant levels from embryos to adulthood, in several head neurons and intestine; MDT-15 binds NHR-49 and NHR-64 in yeast two-hybrid assays, and SBP-1 in GST pull-down assays.

---