Is skn-1 directly regulated by Nrf2?
The presence of predicted SKN-1 binding sites, together with chromatin immunoprecipitation (ChIP) analyses, suggests that most of these detoxification genes are regulated directly by SKN-1 [24,29,30,41,43,44]. Thus, like Nrf2, SKN-1 controls many critical detoxification processes directly.
How are skn-1 and NRF/CNC related?
SKN-1 and Nrf/CNC proteins are most closely related within the DIDLID and DNA-binding regions [6,17]. SKN-1 interacts directly with specific DNA sequences through its BR, which is highly similar to that of Nrf/CNC proteins, and a short element that binds in the minor groove (light blue) [11]. The CNC domain stabilizes these interactions.
What is the function of skn-1?
SKN-1 is the Caenorhabditis elegans ortholog of Nrf2 and other Nrf/CNC proteins. Novel homeostatic and metabolic SKN-1 functions may be applicable to Nrf/CNC proteins. In vivo SKN-1 studies predict considerable complexity in Nrf/CNC regulation. SKN-1 plays a central role in interventions that extend life- and healthspan.
Why is skn-1 phosphorylated by Akt?
Furthermore, SKN-1 is phosphorylated by AKT at multiple positions in vitro and localizes to intestinal nuclei constitutively after mutation of a Ser that both is phosphorylated by AKT, and is predicted at high stringency to be an AKT target [20]. Other evidence indicates that reducing IIS leads to production of ROS that promote SKN-1 activity [98].
What is the function of SKN-1?
During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively. SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress.
What is SKN-1 gene?
SKN-1 also controls other aspects of metabolism. Expression profiling indicates that SKN-1 regulates genes involved in carbohydrate and amino acid metabolism, as well as mitochondrial function [41]. More recently, SKN-1 was shown to be important for mitochondrial biogenesis and health [68].
What is SKN 1B?
SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction.
What does the DAF 16 gene do?
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses.
What does Nrf2 stand for?
The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure.
Where is SKN-1B found?
In contrast, SKN-1B is expressed in two chemosensory neurons, the ASIs, which are thought to act as the worm's hypothalamus, and is constitutively nuclear [3,10,12].
What are ASI neurons?
Aversive stimulus via ASH inhibits ASI activation to nutrients. ASI are a pair of head sensory neurons in C. elegans which are required for satiety behavior and for suppression of food intake.
How does the DAF-2 gene work?
Mutations in daf-2, encoding an insulin receptor-like protein, or age-1, encoding the catalytic subunit of PI3K, increase adult longevity and stress resistance and can cause constitutive developmental arrest as dauer larvae, an alternative third stage larval form that is optimized for long-term survival under harsh ...
How does the DAF-16 gene contribute to aging in the nematode C. elegans?
The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood.
What is DAF 18 gene?
daf-18 represents another example of worm genetics revealing the function of a probable mammalian homolog in the insulin signaling cascade. Genetic analysis has shown that daf-18 functions as a component of the DAF-2 insulin receptor–like signaling pathway that acts downstream of AGE-1 PI3K.