Daf-12

Last updated
Nuclear hormone receptor family member daf-12
Identifiers
Organism Caenorhabditis elegans
Symboldaf-12
Alt. symbolsNR1J1
Entrez 181263
RefSeq (mRNA) NM_001029376.5
RefSeq (Prot) NP_001024547.1
UniProt G5EFF5
Other data
Chromosome X: 10.64 - 10.67 Mb

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]

Related Research Articles

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<i>Caenorhabditis elegans</i> Free-living species of nematode

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.

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COQ7

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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.

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Cynthia Kenyon US molecular biologist

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).

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<span class="mw-page-title-main">Daf-16</span> Ortholog

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.

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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.

Age-1 Gene

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.

References

  1. Kaur S, Jobling S, Jones CS, Noble LR, Routledge EJ, Lockyer AE (7 April 2015). "The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms". PLOS ONE . 10 (4): e0121259. Bibcode:2015PLoSO..1021259K. doi: 10.1371/journal.pone.0121259 . PMC   4388693 . PMID   25849443.
  2. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993). "A C. elegans mutant that lives twice as long as wild type". Nature . 366 (6454): 461–464. Bibcode:1993Natur.366..461K. doi:10.1038/366461a0. PMID   8247153. S2CID   4332206.
  3. Jia K, Albert PS, Riddle DL (2002). "DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity". Development . 129 (1): 221–31. doi:10.1242/dev.129.1.221. PMID   11782415.
  4. Aguilaniu H, Fabrizio P, Witting M (2016). "The Role of Dafachronic Acid Signaling in Development and Longevity in Caenorhabditis elegans: Digging Deeper Using Cutting-Edge Analytical Chemistry". Frontiers in Endocrinology . 7: 12. doi: 10.3389/fendo.2016.00012 . PMC   4749721 . PMID   26903948.
  5. Bento G, Ogawa A, Sommer RJ (July 2010). "Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution". Nature . 466 (7305): 494–7. doi:10.1038/nature09164. PMID   20592728. S2CID   4405326.