Nuclear hormone receptor family member daf-12 | |||||||
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Identifiers | |||||||
Organism | |||||||
Symbol | daf-12 | ||||||
Alt. symbols | NR1J1 | ||||||
Entrez | 181263 | ||||||
RefSeq (mRNA) | NM_001029376.5 | ||||||
RefSeq (Prot) | NP_001024547.1 | ||||||
UniProt | G5EFF5 | ||||||
Other data | |||||||
Chromosome | X: 10.64 - 10.67 Mb | ||||||
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The DAF-12 (abnormal dauer formation protein 12) gene encodes the nuclear receptor of dafachronic acid (a steroid hormone) in the worm Caenorhabditis elegans , with the NRNC Symbol NR1J1 as the homolog of nuclear hormone receptor HR96 (Hr96) in Drosophila melanogaster. [1] DAF-12 has been implicated by Cynthia Kenyon and colleagues in the formation of Dauer larva. [2]
In favorable environments, a cytochrome p450 Daf-9 (Cyp22a1) [3] produce dafachronic acid to binding Daf-12 to initiating downstream gene expression. [4] When in infavorable environments, like starvation, dafachronic acid decreases, Daf-12 will form a complex with co-repressor DIN-1. [5]
The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors, two ligands, a family of seven high-affinity IGF-binding proteins, as well as associated IGFBP degrading enzymes, referred to collectively as proteases.
Caenorhabditis elegans is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek caeno- (recent), rhabditis (rod-like) and Latin elegans (elegant). In 1900, Maupas initially named it Rhabditides elegans. Osche placed it in the subgenus Caenorhabditis in 1952, and in 1955, Dougherty raised Caenorhabditis to the status of genus.
The DAF-2 gene encodes for the insulin-like growth factor 1 (IGF-1) receptor in the worm Caenorhabditis elegans. DAF-2 is part of the first metabolic pathway discovered to regulate the rate of aging. DAF-2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and resistance to bacterial pathogens. Mutations in DAF-2 have been shown by Cynthia Kenyon to double the lifespan of the worms. In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF-2 "the grim reaper gene.”
Mitochondrial 5-demethoxyubiquinone hydroxylase, also known as coenzyme Q7, hydroxylase, is an enzyme that in humans is encoded by the COQ7 gene. The clk-1 (clock-1) gene encodes this protein that is necessary for ubiquinone biosynthesis in the worm Caenorhabditis elegans and other eukaryotes. The mouse version of the gene is called mclk-1 and the human, fruit fly and yeast homolog COQ7.
Dauer describes an alternative developmental stage of nematode worms, particularly rhabditids including Caenorhabditis elegans, whereby the larva goes into a type of stasis and can survive harsh conditions. Since the entrance of the dauer stage is dependent on environmental cues, it represents a classic and well studied example of polyphenism. The dauer state is given other names in the various types of nematodes such as ‘diapause’ or ‘hypobiosis’, but since the C. elegans nematode has become the most studied nematode, the term ‘dauer stage’ or 'dauer larvae' is becoming universally recognised when referring to this state in other free-living nematodes. The dauer stage is also considered to be equivalent to the infective stage of parasitic nematode larvae.
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, cholesterol, and vitamins. These receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and metabolism of the organism.
Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.
Cynthia Jane Kenyon is an American molecular biologist and biogerontologist known for her genetic dissection of aging in a widely used model organism, the roundworm Caenorhabditis elegans. She is the vice president of aging research at Calico Research Labs, and emeritus professor of biochemistry and biophysics at the University of California, San Francisco (UCSF).
Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene.
Gary Bruce Ruvkun is an American molecular biologist at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston. Ruvkun discovered the mechanism by which lin-4, the first microRNA (miRNA) discovered by Victor Ambros, regulates the translation of target messenger RNAs via imperfect base-pairing to those targets, and discovered the second miRNA, let-7, and that it is conserved across animal phylogeny, including in humans. These miRNA discoveries revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Ruvkun also discovered many features of insulin-like signaling in the regulation of aging and metabolism. He was elected a Member of the American Philosophical Society in 2019.
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. It also protects C.elegans during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor DAF-2. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in C. elegans, a successful ageing model organism.
In molecular biology mir-84 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
In molecular biology mir-71 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.
Dafachronic acids are steroid hormones activate the nuclear receptor Daf-12/NR1J1 in Caenorhabditis elegans and related organisms, include Δ4-dafachronic acid and Δ7-dafachronic acid. Both are generated by Daf-9/CYP22A1 from respective precursors.
The Daf-9 gene encodes a cytochrome p450 enzyme catalysis the generation of dafachronic acid in the worm Caenorhabditis elegans, with the CYP Symbol CYP22A1. After generation, dafachronic acid will binding it's nuclear receptor Daf-12 and has been implicated by Cynthia Kenyon and colleagues related to the formation of Dauer larva.
The DAF-1 gene encodes for a cell surface Enzyme-linked receptor of TGF-beta signaling pathway in the worm Caenorhabditis elegans. DAF-1 is one of the type I receptor of TGF-beta pathway. DAF-1 acts as a receptor protein serine/threonine kinase, is activated by type II receptor Daf-4 phosphorylation after the ligand Daf-7 binds to the receptor heterotetramer, and then phosphorylates Daf-8 or Daf-14, the SMAD proteins in C. elegans.
The Dod-13 gene in the worm Caenorhabditis elegans encoding a cytochrome p450 enzyme, which have steroid hydroxylase activity, with the CYP Symbol CYP35B1. Dod-13 is downstream gene of Daf-16 influenced the lifespan of C. elegans.
Cytochrome P450, family 14, also known as CYP14, is a nematoda cytochrome P450 monooxygenase family. The first gene identified in this family is the CYP14A1 from the Caenorhabditis elegans. The function of most genes in this family is unknown.
The age-1 gene is located on chromosome 2 in C.elegans. It gained attention in 1983 for its ability to induce long-lived C. elegans mutants. The age-1 mutant, first identified by Michael Klass, was reported to extend mean lifespan by over 50% at 25 °C when compared to the wild type worm (N2) in 1987 by Johnson et al. Development, metabolism, lifespan, among other processes have been associated with age-1 expression. The age-1 gene is known to share a genetic pathway with daf-2 gene that regulates lifespan in worms. Additionally, both age-1 and daf-2 mutants are dependent on daf-16 and daf-18 genes to promote lifespan extension.