请输入您要查询的百科知识：

　

词条 Nuclear receptor
释义

  1. Species distribution

  2. Ligands

  3. Structure

  4. Mechanism of action

     Type I  Type II  Type III  Type IV 

  5. Coregulatory proteins

      Coactivators    Corepressors  

  6. Agonism vs antagonism

      Agonists    Antagonists    Inverse agonists    Selective receptor modulators  

  7. Alternative mechanisms

      Transrepression    Non-genomic  

  8. Family members

  9. Evolution

  10. History

  11. See also

  12. References

  13. External links

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.

Nuclear receptors have the ability to directly bind to DNA and regulate the expression of adjacent genes, hence these receptors are classified as transcription factors.[2][3] The regulation of gene expression by nuclear receptors generally only happens when a ligand — a molecule that affects the receptor's behavior — is present. More specifically, ligand binding to a nuclear receptor results in a conformational change in the receptor, which, in turn, activates the receptor, resulting in up- or down-regulation of gene expression.

A unique property of nuclear receptors that differentiates them from other classes of receptors is their ability to directly interact with and control the expression of genomic DNA. As a consequence, nuclear receptors play key roles in both embryonic development and adult homeostasis. As discussed below, nuclear receptors may be classified according to either mechanism[4][5] or homology.[6][7]

Species distribution

Nuclear receptors are specific to metazoans (animals) and are not found in protists, algae, fungi, or plants.[8] Amongst the early-branching animal lineages with sequenced genomes, two have been reported from the sponge Amphimedon queenslandica, two from the ctenophore Mnemiopsis leidyi[9] four from the placozoan Trichoplax adhaerens and 17 from the cnidarian Nematostella vectensis.[10] There are 270 nuclear receptors in the nematode C. elegans alone.[11] Humans, mice, and rats have respectively 48, 49, and 47 nuclear receptors each.[12]

Ligands

Ligands that bind to and activate nuclear receptors include lipophilic substances such as endogenous hormones, vitamins A and D, and xenobiotic endocrine disruptors. Because the expression of a large number of genes is regulated by nuclear receptors, ligands that activate these receptors can have profound effects on the organism. Many of these regulated genes are associated with various diseases, which explains why the molecular targets of approximately 13% of U.S. Food and Drug Administration (FDA) approved drugs target nuclear receptors.[13]

A number of nuclear receptors, referred to as orphan receptors,[14] have no known (or at least generally agreed upon) endogenous ligands. Some of these receptors such as FXR, LXR, and PPAR bind a number of metabolic intermediates such as fatty acids, bile acids and/or sterols with relatively low affinity. These receptors hence may function as metabolic sensors. Other nuclear receptors, such as CAR and PXR appear to function as xenobiotic sensors up-regulating the expression of cytochrome P450 enzymes that metabolize these xenobiotics.[15]

{{Clear}}

Structure

Most nuclear receptors have molecular masses between 50,000 and 100,000 daltons.

Nuclear receptors are modular in structure and contain the following domains:[16][17]

  • (A-B) N-terminal regulatory domain: Contains the activation function 1 (AF-1) whose action is independent of the presence of ligand.[18] The transcriptional activation of AF-1 is normally very weak, but it does synergize with AF-2 in the E-domain (see below) to produce a more robust upregulation of gene expression. The A-B domain is highly variable in sequence between various nuclear receptors.
  • (C) DNA-binding domain (DBD): Highly conserved domain containing two zinc fingers that binds to specific sequences of DNA called hormone response elements (HRE).
  • (D) Hinge region: Thought to be a flexible domain that connects the DBD with the LBD. Influences intracellular trafficking and subcellular distribution.
  • (E) Ligand binding domain (LBD): Moderately conserved in sequence and highly conserved in structure between the various nuclear receptors. The structure of the LBD is referred to as an alpha helical sandwich fold in which three anti parallel alpha helices (the "sandwich filling") are flanked by two alpha helices on one side and three on the other (the "bread"). The ligand binding cavity is within the interior of the LBD and just below three anti parallel alpha helical sandwich "filling". Along with the DBD, the LBD contributes to the dimerization interface of the receptor and in addition, binds coactivator and corepressor proteins. The LBD also contains the activation function 2 (AF-2) whose action is dependent on the presence of bound ligand.[18]
  • (F) C-terminal domain: Highly variable in sequence between various nuclear receptors.

The N-terminal (A/B), DNA-binding (C), and ligand binding (E) domains are independently well folded and structurally stable while the hinge region (D) and optional C-terminal (F) domains may be conformationally flexible and disordered.[20] Domains relative orientations are very different by comparing three known multi-domain crystal structures, two of them binding on DR1,[1][22] one binding on DR4.[1]

{{Pfam_box Symbol = zf-C4 Name = DNA binding domain (DBD) image = PR_DBD_2C7A.png width = caption = Crystallographic structure of the human progesterone receptor DNA-binding domain dimer (cyan and green) complexed with double stranded DNA (magenta). Zinc atoms of are depicted as grey spheres.[24] Pfam = PF00105 InterPro = IPR001628 SMART = SM00399 PROSITE = PDOC00031 SCOP = 1hra TCDB = OPM family = OPM protein = CDD = cd06916
}}		{{Pfam_box Symbol = Hormone_recep Name = Ligand-binding domain (LBD) image = RORC_3L0L.png width = caption = Crystallographic structure of the ligand binding domain of the human RORγ (rainbow colored, N-terminus = blue, C-terminus = red) complexed with 25-hydroxycholesterol (space-filling model (carbon = white, oxygen = red) and the NCOA2 coactivator (magneta).[25] Pfam = PF00104 InterPro = IPR000536 SMART = SM00430 PROSITE = SCOP = 1lbd TCDB = OPM family = OPM protein = CDD = cd06157
}}
{{Clear}}

Mechanism of action

Nuclear receptors are multifunctional proteins that transduce signals of their cognate ligands. Nuclear receptors (NRs) may be classified into two broad classes according to their mechanism of action and subcellular distribution in the absence of ligand.

Small lipophilic substances such as natural hormones diffuse through the cell membrane and bind to nuclear receptors located in the cytosol (type I NR) or nucleus (type II NR) of the cell. Binding causes a conformational change in the receptor which, depending on the class of receptor, triggers a cascade of downstream events that direct the NRs to DNA transcription regulation sites which result in up or down-regulation of gene expression. They generally function as homo/heterodimers.[2] In addition, two additional classes, type III which are a variant of type I, and type IV that bind DNA as monomers have also been identified.[4]

Accordingly, nuclear receptors may be subdivided into the following four mechanistic classes:[4][5]

Type I

Ligand binding to type I nuclear receptors in the cytosol results in the dissociation of heat shock proteins, homo-dimerization, translocation (i.e., active transport) from the cytoplasm into the cell nucleus, and binding to specific sequences of DNA known as hormone response elements (HREs). Type I nuclear receptors bind to HREs consisting of two half-sites separated by a variable length of DNA, and the second half-site has a sequence inverted from the first (inverted repeat). Type I nuclear receptors include members of subfamily 3, such as the androgen receptor, estrogen receptors, glucocorticoid receptor, and progesterone receptor.[30]

It has been noted that some of the NR subfamily 2 nuclear receptors may bind to direct repeat instead of inverted repeat HREs. In addition, some nuclear receptors that bind either as monomers or dimers, with only a single DNA binding domain of the receptor attaching to a single half site HRE. These nuclear receptors are considered orphan receptors, as their endogenous ligands are still unknown.

The nuclear receptor/DNA complex then recruits other proteins that transcribe DNA downstream from the HRE into messenger RNA and eventually protein, which causes a change in cell function.

Type II

Type II receptors, in contrast to type I, are retained in the nucleus regardless of the ligand binding status and in addition bind as hetero-dimers (usually with RXR) to DNA.[2] In the absence of ligand, type II nuclear receptors are often complexed with corepressor proteins. Ligand binding to the nuclear receptor causes dissociation of corepressor and recruitment of coactivator proteins. Additional proteins including RNA polymerase are then recruited to the NR/DNA complex that transcribe DNA into messenger RNA.

Type II nuclear receptors include principally subfamily 1, for example the retinoic acid receptor, retinoid X receptor and thyroid hormone receptor.[32]

Type III

Type III nuclear receptors (principally NR subfamily 2) are similar to type I receptors in that both classes bind to DNA as homodimers. However, type III nuclear receptors, in contrast to type I, bind to direct repeat instead of inverted repeat HREs.

Type IV

Type IV nuclear receptors bind either as monomers or dimers, but only a single DNA binding domain of the receptor binds to a single half site HRE. Examples of type IV receptors are found in most of the NR subfamilies.

Coregulatory proteins

{{main|nuclear receptor coregulators}}

Nuclear receptors bound to hormone response elements recruit a significant number of other proteins (referred to as transcription coregulators) that facilitate or inhibit the transcription of the associated target gene into mRNA.[33] The function of these coregulators are varied and include chromatin remodeling (making the target gene either more or less accessible to transcription) or a bridging function to stabilize the binding of other coregulatory proteins. Nuclear receptors may bind specifically to a number of coregulator proteins, and thereby influence cellular mechanisms of signal transduction both directly, as well as indirectly.[3]

Coactivators

Binding of agonist ligands (see section below) to nuclear receptors induces a conformation of the receptor that preferentially binds coactivator proteins. These proteins often have an intrinsic histone acetyltransferase (HAT) activity, which weakens the association of histones to DNA, and therefore promotes gene transcription.

Corepressors

Binding of antagonist ligands to nuclear receptors in contrast induces a conformation of the receptor that preferentially binds corepressor proteins. These proteins, in turn, recruit histone deacetylases (HDACs), which strengthens the association of histones to DNA, and therefore represses gene transcription.

Agonism vs antagonism

Depending on the receptor involved, the chemical structure of the ligand and the tissue that is being affected, nuclear receptor ligands may display dramatically diverse effects ranging in a spectrum from agonism to antagonism to inverse agonism.[38]

Agonists

The activity of endogenous ligands (such as the hormones estradiol and testosterone) when bound to their cognate nuclear receptors is normally to upregulate gene expression. This stimulation of gene expression by the ligand is referred to as an agonist response. The agonistic effects of endogenous hormones can also be mimicked by certain synthetic ligands, for example, the glucocorticoid receptor anti-inflammatory drug dexamethasone. Agonist ligands work by inducing a conformation of the receptor which favors coactivator binding (see upper half of the figure to the right).

Antagonists

Other synthetic nuclear receptor ligands have no apparent effect on gene transcription in the absence of endogenous ligand. However they block the effect of agonist through competitive binding to the same binding site in the nuclear receptor. These ligands are referred to as antagonists. An example of antagonistic nuclear receptor drug is mifepristone which binds to the glucocorticoid and progesterone receptors and therefore blocks the activity of the endogenous hormones cortisol and progesterone respectively. Antagonist ligands work by inducing a conformation of the receptor which prevents coactivator and promotes corepressor binding (see lower half of the figure to the right).

Inverse agonists

Finally, some nuclear receptors promote a low level of gene transcription in the absence of agonists (also referred to as basal or constitutive activity). Synthetic ligands which reduce this basal level of activity in nuclear receptors are known as inverse agonists.[39]

Selective receptor modulators

A number of drugs that work through nuclear receptors display an agonist response in some tissues and an antagonistic response in other tissues. This behavior may have substantial benefits since it may allow retaining the desired beneficial therapeutic effects of a drug while minimizing undesirable side effects. Drugs with this mixed agonist/antagonist profile of action are referred to as selective receptor modulators (SRMs). Examples include Selective Androgen Receptor Modulators (SARMs), Selective Estrogen Receptor Modulators (SERMs) and Selective Progesterone Receptor Modulators (SPRMs). The mechanism of action of SRMs may vary depending on the chemical structure of the ligand and the receptor involved, however it is thought that many SRMs work by promoting a conformation of the receptor that is closely balanced between agonism and antagonism. In tissues where the concentration of coactivator proteins is higher than corepressors, the equilibrium is shifted in the agonist direction. Conversely in tissues where corepressors dominate, the ligand behaves as an antagonist.[40]

Alternative mechanisms

Transrepression

The most common mechanism of nuclear receptor action involves direct binding of the nuclear receptor to a DNA hormone response element. This mechanism is referred to as transactivation. However some nuclear receptors not only have the ability to directly bind to DNA, but also to other transcription factors. This binding often results in deactivation of the second transcription factor in a process known as transrepression.[41] One example of a nuclear receptor that are able to transrepress is the glucocorticoid receptor (GR). Furthermore, certain GR ligands known as Selective Glucocorticoid Receptor Agonists (SEGRAs) are able to activate GR in such a way that GR more strongly transrepresses than transactivates. This selectivity increases the separation between the desired antiinflammatory effects and undesired metabolic side effects of these selective glucocorticoids.

Non-genomic

The classical direct effects of nuclear receptors on gene regulation normally take hours before a functional effect is seen in cells because of the large number of intermediate steps between nuclear receptor activation and changes in protein expression levels. However it has been observed that many effects of the application of nuclear hormones, such as changes in ion channel activity, occur within minutes which is inconsistent with the classical mechanism of nuclear receptor action. While the molecular target for these non-genomic effects of nuclear receptors has not been conclusively demonstrated, it has been hypothesized that there are variants of nuclear receptors which are membrane associated instead of being localized in the cytosol or nucleus. Furthermore, these membrane associated receptors function through alternative signal transduction mechanisms not involving gene regulation.[42][43]

While it has been hypothesized that there are several membrane associated receptors for nuclear hormones, many of the rapid effects have been shown to require canonical nuclear receptors.[44][45] However, testing the relative importance of the genomic and nongenomic mechanisms in vivo has been prevented by the absence of specific molecular mechanisms for the nongenomic effects that could be blocked by mutation of the receptor without disrupting its direct effects on gene expression.

A molecular mechanism for non-genomic signaling through the nuclear thyroid hormone receptor TRβ involves the phosphatidylinositol 3-kinase (PI3K).[46] This signaling can be blocked by a single tyrosine to phenylalanine substitution in TRβ without disrupting direct gene regulation.[47] When mice were created with this single, conservative amino acid substitution in TRβ,[47] synaptic maturation and plasticity in the hippocampus was impaired almost as effectively as completely blocking thyroid hormone synthesis.[49] This mechanism appears to be conserved in all mammals but not in TRα or any other nuclear receptors. Thus, phosphotyrosine-dependent association of TRβ with PI3K provides a potential mechanism for integrating regulation of development and metabolism by thyroid hormone and receptor tyrosine kinases. In addition, thyroid hormone signaling through PI3K can alter gene expression.[50]

Family members

The following is a list of the 48 known human nuclear receptors plus selected non-human receptors[12] categorized according to sequence homology.[6][7]

{{Clear}}
SubfamilyGroupMember
NRNC Symbol[6] Abbreviation Name Gene Ligand(s)
1Thyroid Hormone Receptor-likeAThyroid hormone receptorNR1A1TRαThyroid hormone receptor-α{{Gene|THRA}}thyroid hormone
NR1A2TRβThyroid hormone receptor-β{{Gene|THRB}}
BRetinoic acid receptor NR1B1 RARα Retinoic acid receptor-αRARA}}vitamin A and related compounds
NR1B2 RARβ Retinoic acid receptor-βRARB}}
NR1B3 RARγ Retinoic acid receptor-γRARG}}
CPeroxisome proliferator-activated receptorNR1C1 PPARα Peroxisome proliferator-activated receptor-αPPARA}}fatty acids, prostaglandins
NR1C2 PPAR-β/δ Peroxisome proliferator-activated receptor-β/δPPARD}}
NR1C3 PPARγ Peroxisome proliferator-activated receptor-γPPARG}}
DRev-ErbA NR1D1 Rev-ErbAα Rev-ErbAαNR1D1}}heme
NR1D2 Rev-ErbAβ Rev-ErbAαNR1D2}}
FRAR-related orphan receptorNR1F1RORαRAR-related orphan receptor-α{{Gene|RORA}}cholesterol, ATRA
NR1F2 RORβ RAR-related orphan receptor-βRORB}}
NR1F3 RORγ RAR-related orphan receptor-γRORC}}
HLiver X receptor-like NR1H3 LXRα Liver X receptor-αNR1H3}}oxysterols
NR1H2 LXRβ Liver X receptor-βNR1H2}}
NR1H4 FXR Farnesoid X receptorNR1H4}}
NR1H5[4] FXR-β Farnesoid X receptor-βNR1H5P}}
IVitamin D receptor-likeNR1I1VDRVitamin D receptor{{Gene|VDR}}vitamin D
NR1I2 PXR Pregnane X receptorNR1I2}} xenobiotics
NR1I3 CAR Constitutive androstane receptorNR1I3}} androstane
XNRs with two DNA binding domains[56][57] NR1X1 2DBD-NRα
NR1X2 2DBD-NRβ
NR1X3 2DBD-NRγ
2Retinoid X Receptor-likeAHepatocyte nuclear factor-4NR2A1HNF4αHepatocyte nuclear factor-4-α{{Gene|HNF4A}}fatty acids
NR2A2 HNF4γ Hepatocyte nuclear factor-4-γHNF4G}}
BRetinoid X receptor NR2B1 RXRα Retinoid X receptor-αRXRA}}retinoids
NR2B2 RXRβ Retinoid X receptor-βRXRB}}
NR2B3 RXRγ Retinoid X receptor-γRXRG}}
CTesticular receptorNR2C1TR2Testicular receptor 2{{Gene|NR2C1}}
NR2C2 TR4 Testicular receptor 4NR2C2}}
ETLX/PNR NR2E1 TLX Homologue of the Drosophila tailless geneNR2E1}}
NR2E3 PNR Photoreceptor cell-specific nuclear receptorNR2E3}}
FCOUP/EARNR2F1COUP-TFIChicken ovalbumin upstream promoter-transcription factor I{{Gene|NR2F1}}
NR2F2 COUP-TFII Chicken ovalbumin upstream promoter-transcription factor IINR2F2}}
NR2F6 EAR-2V-erbA-relatedNR2F6}}
3Estrogen Receptor-likeAEstrogen receptorNR3A1ERαEstrogen receptor-α{{Gene|ESR1}}estrogens
NR3A2 ERβ Estrogen receptor-βESR2}}
BEstrogen related receptor NR3B1 ERRα Estrogen-related receptor-αESRRA}}
NR3B2 ERRβ Estrogen-related receptor-βESRRB}}
NR3B3 ERRγ Estrogen-related receptor-γESRRG}}
C3-Ketosteroid receptorsNR3C1GRGlucocorticoid receptor{{Gene|NR3C1}}cortisol
NR3C2 MR Mineralocorticoid receptorNR3C2}} aldosterone
NR3C3 PR Progesterone receptorPGR}} progesterone
NR3C4 AR Androgen receptorAR}} testosterone
4Nerve Growth Factor IB-likeANGFIB/NURR1/NOR1NR4A1NGFIBNerve Growth factor IB{{Gene|NR4A1}}
NR4A2 NURR1 Nuclear receptor related 1NR4A2}}
NR4A3 NOR1 Neuron-derived orphan receptor 1NR4A3}}
5Steroidogenic Factor-likeASF1/LRH1NR5A1SF1Steroidogenic factor 1{{Gene|NR5A1}}phosphatidylinositols
NR5A2 LRH-1 Liver receptor homolog-1NR5A2}} phosphatidylinositols
6Germ Cell Nuclear Factor-likeAGCNFNR6A1GCNFGerm cell nuclear factor{{Gene|NR6A1}}
0MiscellaneousBDAX/SHPNR0B1DAX1Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1{{Gene|NR0B1}}
NR0B2 SHP Small heterodimer partnerNR0B2}}

Evolution

A topic of debate has been on the identity of the ancestral nuclear receptor as either a ligand-binding or an orphan receptor. This debate began more than twenty-five years ago when the first ligands were identified as mammalian steroid and thyroid hormones.[5] Shortly thereafter, the identification of the ecdysone receptor in Drosophila introduced the idea that nuclear receptors were hormonal receptors that bind ligands with a nanomolar affinity. At the time, the three known nuclear receptor ligands were steroids, retinoids, and thyroid hormone, and of those three, both steroids and retinoids were products of terpenoid metabolism. Thus, it was postulated that ancestral receptor would have been liganded by a terpenoid molecule.[6]

In 1992, a comparison of the DNA-binding domain of all known nuclear receptors led to the construction of a phylogenic tree of nuclear receptor that indicated that all nuclear receptors shared a common ancestor.[7] As a result, there was an increased effort upon uncovering the state of the first nuclear receptor, and by 1997 an alternative hypothesis was suggested: the ancestral nuclear receptor was an orphan receptor and it acquired ligand-binding ability over time[8] This hypothesis was proposed based on the following arguments:

  1. The nuclear receptor sequences that had been identified in the earliest metazoans (cnidarians and Schistosoma) were all members of the COUP-TF, RXR, and FTZ-F1 groups of receptors. Both COUP-TF and FTZ-F1 are orphan receptors, and RXR is only found to bind a ligand in vertebrates.&91;9&93;
  2. While orphan receptors had known arthropod homologs, no orthologs of liganded vertebrate receptors had been identified outside vertebrates, suggesting that orphan receptors are older than liganded-receptors.&91;10&93;
  3. Orphan receptors are found amongst all six subfamilies of nuclear receptors, while ligand-dependent receptors are found amongst three.&91;8&93; Thus, since the ligand-dependent receptors were believed to be predominantly member of recent subfamilies, it seemed logical that they gained the ability to bind ligands independently.
  4. The phylogenetic position of a given nuclear receptor within the tree correlates to its DNA-binding domain and dimerization abilities, but there is no identified relationship between a ligand-dependent nuclear receptor and the chemical nature of its ligand. In addition to this, the evolutionary relationships between ligand-dependent receptors did not make much sense as closely related receptors of subfamilies bound ligands originating from entirely different biosynthetic pathways (e.g. TRs and RARs). On the other hand, subfamilies that are not evolutionarily related bind similar ligands (RAR and RXR both bind all-trans and 9-cis retinoic acid respectively).&91;10&93;
  5. In 1997, it was discovered that nuclear receptors did not exist in static off and on conformations, but that a ligand could alter the equilibrium between the two states. Furthermore, it was found that nuclear receptors could be regulated in a ligand-independent manner, through either phosphorylation or other post-translational modifications. Thus, this provided a mechanism for how an ancestral orphan receptor was regulated in a ligand-independent manner, and explained why the ligand binding domain was conserved.&91;10&93;

Over the next 10 years, experiments were conducted to test this hypothesis and counterarguments soon emerged:

  1. Nuclear receptors were identified in the newly sequenced genome of the demosponge Amphimedon queenslandica, a member Porifera, the most ancient metazoan phylum. The A. queenslandica genome contains two nuclear receptors known as AqNR1 and AqNR2 and both were characterized to bind and be regulated by ligands.&91;11&93;
  2. Homologs for ligand-dependent vertebrate receptors were found outside vertebrates in mollusks and Platyhelminthes. Furthermore, the nuclear receptors found in cnidarians were found to have structural ligands in mammals, which could mirror the ancestral situation.
  3. Two putative orphan receptors, HNF4 and USP were found, via structural and mass spectrometry analysis, to bind fatty acids and phospholipids respectively.&91;12&93;
  4. Nuclear receptors and ligands are found to be a lot less specific than was previously thought. Retinoids can bind mammalian receptors other than RAR and RXR such as, PPAR, RORb, or COUP-TFII. Furthermore, RXR is sensitive to a wide range of molecules including retinoids, fatty acids, and phospholipids.&91;13&93;
  5. Study of steroid receptor evolution revealed that the ancestral steroid receptor could bind a ligand, estradiol. Conversely, the estrogen receptor found in mollusks is constitutively active and did not bind estrogen-related hormones. Thus, this provided an example of how an ancestral ligand-dependent receptor could lose its ability to bind ligands.&91;14&93;

A combination of this recent evidence, as well as an in-depth study of the physical structure of the nuclear receptor ligand binding domain has led to the emergence of a new hypothesis regarding the ancestral state of the nuclear receptor. This hypothesis suggests that the ancestral receptor may act as a lipid sensor with an ability to bind, albeit rather weakly, several different hydrophobic molecules such as, retinoids, steroids, hemes, and fatty acids. With its ability to interact with a variety of compounds, this receptor, through duplications, would either lose its ability for ligand-dependent activity, or specialize into a highly specific receptor for a particular molecule.[13]

History

Below is a brief selection of key events in the history of nuclear receptor research.[72]

  • 1905 – Ernest Starling coined the word hormone
  • 1926 – Edward Calvin Kendall and Tadeus Reichstein isolated and determined the structures of cortisone and thyroxine
  • 1929 – Adolf Butenandt and Edward Adelbert Doisy – independently isolated and determined the structure of estrogen
  • 1958 – Elwood Jensen – isolated the estrogen receptor
  • 1980s – cloning of the estrogen, glucocorticoid, and thyroid hormone receptors by Pierre Chambon, Ronald Evans, and Björn Vennström respectively
  • 2004 – Pierre Chambon, Ronald Evans, and Elwood Jensen were awarded the Albert Lasker Award for Basic Medical Research, an award that frequently precedes a Nobel Prize in Medicine

See also

  • NucleaRDB
  • Obesogen
  • Steroid hormone receptor

References

1. ^{{cite journal | vauthors = Lou X, Toresson G, Benod C, Suh JH, Philips KJ, Webb P, Gustafsson JA | title = Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA | journal = Nature Structural & Molecular Biology | volume = 21 | issue = 3 | pages = 277–81 | date = March 2014 | pmid = 24561505 | doi = 10.1038/nsmb.2778 }}
2. ^1 {{cite journal | vauthors = Amoutzias GD, Pichler EE, Mian N, De Graaf D, Imsiridou A, Robinson-Rechavi M, Bornberg-Bauer E, Robertson DL, Oliver SG | title = A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network | journal = BMC Systems Biology | volume = 1 | pages = 34 | date = July 2007 | pmid = 17672894 | pmc = 1971058 | doi = 10.1186/1752-0509-1-34 }}
3. ^{{cite journal | vauthors = Copland JA, Sheffield-Moore M, Koldzic-Zivanovic N, Gentry S, Lamprou G, Tzortzatou-Stathopoulou F, Zoumpourlis V, Urban RJ, Vlahopoulos SA | title = Sex steroid receptors in skeletal differentiation and epithelial neoplasia: is tissue-specific intervention possible? | journal = BioEssays | volume = 31 | issue = 6 | pages = 629–41 | date = June 2009 | pmid = 19382224 | doi = 10.1002/bies.200800138 }}
4. ^{{cite journal | vauthors = Otte K, Kranz H, Kober I, Thompson P, Hoefer M, Haubold B, Remmel B, Voss H, Kaiser C, Albers M, Cheruvallath Z, Jackson D, Casari G, Koegl M, Pääbo S, Mous J, Kremoser C, Deuschle U | title = Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol | journal = Molecular and Cellular Biology | volume = 23 | issue = 3 | pages = 864–72 | date = February 2003 | pmid = 12529392 | pmc = 140718 | doi = 10.1128/mcb.23.3.864-872.2003 }}
5. ^{{cite journal | vauthors = Evans RM | title = The steroid and thyroid hormone receptor superfamily | journal = Science | volume = 240 | issue = 4854 | pages = 889–95 | date = May 1988 | pmid = 3283939 | pmc = 6159881 | doi = 10.1126/science.3283939 | via = }}
6. ^{{cite journal | vauthors = Moore DD | title = Diversity and unity in the nuclear hormone receptors: a terpenoid receptor superfamily | journal = The New Biologist | volume = 2 | issue = 1 | pages = 100–5 | date = January 1990 | pmid = 1964083 }}
7. ^{{cite journal | vauthors = Laudet V, Hänni C, Coll J, Catzeflis F, Stéhelin D | title = Evolution of the nuclear receptor gene superfamily | journal = The EMBO Journal | volume = 11 | issue = 3 | pages = 1003–13 | date = March 1992 | pmid = 1312460 | pmc = 556541 | doi = 10.1002/j.1460-2075.1992.tb05139.x }}
8. ^1 2 3 {{cite journal | vauthors = Laudet V | title = Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor | journal = Journal of Molecular Endocrinology | volume = 19 | issue = 3 | pages = 207–26 | date = December 1997 | pmid = 9460643 | doi = 10.1677/jme.0.0190207 }}
9. ^{{cite journal | vauthors = Escriva H, Safi R, Hänni C, Langlois MC, Saumitou-Laprade P, Stehelin D, Capron A, Pierce R, Laudet V | title = Ligand binding was acquired during evolution of nuclear receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 13 | pages = 6803–8 | date = June 1997 | pmid = 9192646 | doi = 10.1073/pnas.94.13.6803 | url = http://www.pnas.org/content/94/13/6803.full.pdf | pmc=21239}}
10. ^1 2 {{cite journal | vauthors = Escriva H, Delaunay F, Laudet V | title = Ligand binding and nuclear receptor evolution | journal = BioEssays | volume = 22 | issue = 8 | pages = 717–27 | date = August 2000 | pmid = 10918302 | doi = 10.1002/1521-1878(200008)22:8<717::AID-BIES5>3.0.CO;2-I }}
11. ^{{cite journal | vauthors = Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW | title = Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor | journal = PLoS Biology | volume = 8 | issue = 10 | pages = e1000497 | date = October 2010 | pmid = 20957188 | doi = 10.1371/journal.pbio.1000497 | pmc=2950128}}
12. ^{{cite journal | vauthors = Schwabe JW, Teichmann SA | title = Nuclear receptors: the evolution of diversity | journal = Science's STKE | volume = 2004 | issue = 217 | pages = pe4 | date = January 2004 | pmid = 14747695 | doi = 10.1126/stke.2172004pe4 }}
13. ^1 {{cite journal | vauthors = Markov GV, Laudet V | title = Origin and evolution of the ligand-binding ability of nuclear receptors | journal = Molecular and Cellular Endocrinology | volume = 334 | issue = 1–2 | pages = 21–30 | date = March 2011 | pmid = 21055443 | doi = 10.1016/j.mce.2010.10.017 | series = Evolution of Nuclear Hormone Receptors }}
14. ^{{cite journal | vauthors = Thornton JW, Need E, Crews D | title = Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling | journal = Science | volume = 301 | issue = 5640 | pages = 1714–7 | date = September 2003 | pmid = 14500980 | doi = 10.1126/science.1086185 }}
15. ^1 {{cite journal | vauthors = Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V | title = International Union of Pharmacology. LXVI. Orphan nuclear receptors | journal = Pharmacological Reviews | volume = 58 | issue = 4 | pages = 798–836 | date = December 2006 | pmid = 17132856 | doi = 10.1124/pr.58.4.10 }}
16. ^1 {{cite journal | vauthors = Björnström L, Sjöberg M | title = Estrogen receptor-dependent activation of AP-1 via non-genomic signalling | journal = Nuclear Receptor | volume = 2 | issue = 1 | pages = 3 | date = June 2004 | pmid = 15196329 | pmc = 434532 | doi = 10.1186/1478-1336-2-3 }}
17. ^1 {{cite journal | vauthors = Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW | title = Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor | journal = PLoS Biology | volume = 8 | issue = 10 | pages = e1000497 | date = October 2010 | pmid = 20957188 | pmc = 2950128 | doi = 10.1371/journal.pbio.1000497 }}
18. ^1 {{cite journal | vauthors = Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engström O, Ohman L, Greene GL, Gustafsson JA, Carlquist M | title = Molecular basis of agonism and antagonism in the oestrogen receptor | journal = Nature | volume = 389 | issue = 6652 | pages = 753–8 | date = October 1997 | pmid = 9338790 | doi = 10.1038/39645 }}
19. ^1 {{cite journal | vauthors = Busch BB, Stevens WC, Martin R, Ordentlich P, Zhou S, Sapp DW, Horlick RA, Mohan R | title = Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor alpha | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 23 | pages = 5593–6 | date = November 2004 | pmid = 15509154 | doi = 10.1021/jm049334f }}
20. ^1 2 {{PDB|3E00}}; {{cite journal | vauthors = Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, Rastinejad F | title = Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA | journal = Nature | volume = 456 | issue = 7220 | pages = 350–6 | date = November 2008 | pmid = 19043829 | pmc = 2743566 | doi = 10.1038/nature07413 }}
21. ^1 {{cite journal | vauthors = Chandra V, Huang P, Potluri N, Wu D, Kim Y, Rastinejad F | title = Multidomain integration in the structure of the HNF-4α nuclear receptor complex | journal = Nature | volume = 495 | issue = 7441 | pages = 394–8 | date = March 2013 | pmid = 23485969 | pmc = 3606643 | doi = 10.1038/nature11966 }}
22. ^1 {{cite journal | vauthors = Escriva H, Langlois MC, Mendonça RL, Pierce R, Laudet V | title = Evolution and diversification of the nuclear receptor superfamily | journal = Annals of the New York Academy of Sciences | volume = 839 | issue = | pages = 143–6 | date = May 1998 | pmid = 9629140 | doi = 10.1111/j.1749-6632.1998.tb10747.x }}
23. ^1 {{cite journal | vauthors = Evans RM | title = The steroid and thyroid hormone receptor superfamily | journal = Science | volume = 240 | issue = 4854 | pages = 889–95 | date = May 1988 | pmid = 3283939 | doi = 10.1126/science.3283939 }}
24. ^1 {{cite journal | vauthors = Gilbert ME | title = Alterations in synaptic transmission and plasticity in area CA1 of adult hippocampus following developmental hypothyroidism | journal = Brain Research. Developmental Brain Research | volume = 148 | issue = 1 | pages = 11–8 | date = January 2004 | pmid = 14757514 | doi = 10.1016/j.devbrainres.2003.09.018 | url = https://zenodo.org/record/1258893 }}
25. ^1 {{cite journal | vauthors = Glass CK, Rosenfeld MG | title = The coregulator exchange in transcriptional functions of nuclear receptors | journal = Genes & Development | volume = 14 | issue = 2 | pages = 121–41 | date = January 2000 | pmid = 10652267 | doi = 10.1101/gad.14.2.121 | url = http://genesdev.cshlp.org/content/14/2/121.long | doi-broken-date = 2019-03-16 }}
26. ^1 {{cite journal | vauthors = Gronemeyer H, Gustafsson JA, Laudet V | title = Principles for modulation of the nuclear receptor superfamily | journal = Nature Reviews. Drug Discovery | volume = 3 | issue = 11 | pages = 950–64 | date = November 2004 | pmid = 15520817 | doi = 10.1038/nrd1551 }}
27. ^1 {{PDB|3L0L}}; {{cite journal | vauthors = Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y | title = Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma | journal = Molecular Endocrinology | volume = 24 | issue = 5 | pages = 923–9 | date = May 2010 | pmid = 20203100 | pmc = 2870936 | doi = 10.1210/me.2009-0507 }}
28. ^1 {{cite journal | vauthors = Klinge CM, Bodenner DL, Desai D, Niles RM, Traish AM | title = Binding of type II nuclear receptors and estrogen receptor to full and half-site estrogen response elements in vitro | journal = Nucleic Acids Research | volume = 25 | issue = 10 | pages = 1903–12 | date = May 1997 | pmid = 9115356 | pmc = 146682 | doi = 10.1093/nar/25.10.1903 }}
29. ^1 {{cite journal | vauthors = Klinge CM | title = Estrogen receptor interaction with co-activators and co-repressors | journal = Steroids | volume = 65 | issue = 5 | pages = 227–51 | date = May 2000 | pmid = 10751636 | doi = 10.1016/S0039-128X(99)00107-5 }}
30. ^1 {{cite journal | vauthors = Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC | title = Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity | journal = Cell | volume = 104 | issue = 5 | pages = 719–30 | date = March 2001 | pmid = 11257226 | doi = 10.1016/S0092-8674(01)00268-9 }}
31. ^1 {{cite journal | vauthors = Kumar R, Thompson EB | title = The structure of the nuclear hormone receptors | journal = Steroids | volume = 64 | issue = 5 | pages = 310–9 | date = May 1999 | pmid = 10406480 | doi = 10.1016/S0039-128X(99)00014-8 }}
32. ^{{cite journal | vauthors = Laudet V | title = Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor | journal = Journal of Molecular Endocrinology | volume = 19 | issue = 3 | pages = 207–26 | date = December 1997 | pmid = 9460643 | doi = 10.1677/jme.0.0190207 }}
33. ^1 {{cite journal | vauthors = Linja MJ, Porkka KP, Kang Z, Savinainen KJ, Jänne OA, Tammela TL, Vessella RL, Palvimo JJ, Visakorpi T | title = Expression of androgen receptor coregulators in prostate cancer | journal = Clinical Cancer Research | volume = 10 | issue = 3 | pages = 1032–40 | date = February 2004 | pmid = 14871982 | doi = 10.1158/1078-0432.CCR-0990-3 }}
34. ^1 2 3 {{cite journal | vauthors = Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM | title = The nuclear receptor superfamily: the second decade | journal = Cell | volume = 83 | issue = 6 | pages = 835–9 | date = December 1995 | pmid = 8521507 | pmc = 6159888 | doi = 10.1016/0092-8674(95)90199-X }}
35. ^1 2 {{cite journal | vauthors = Martin NP, Marron Fernandez de Velasco E, Mizuno F, Scappini EL, Gloss B, Erxleben C, Williams JG, Stapleton HM, Gentile S, Armstrong DL | title = A rapid cytoplasmic mechanism for PI3 kinase regulation by the nuclear thyroid hormone receptor, TRβ, and genetic evidence for its role in the maturation of mouse hippocampal synapses in vivo | journal = Endocrinology | volume = 155 | issue = 9 | pages = 3713–24 | date = September 2014 | pmid = 24932806 | pmc = 4138568 | doi = 10.1210/en.2013-2058 }}
36. ^1 {{cite journal | vauthors = Moeller LC, Broecker-Preuss M | title = Transcriptional regulation by nonclassical action of thyroid hormone | journal = Thyroid Research | volume = 4 Suppl 1 | issue = | pages = S6 | date = August 2011 | pmid = 21835053 | pmc = 3155112 | doi = 10.1186/1756-6614-4-S1-S6 }}
37. ^1 {{cite journal | vauthors = Mohan R, Heyman RA | title = Orphan nuclear receptor modulators | journal = Current Topics in Medicinal Chemistry | volume = 3 | issue = 14 | pages = 1637–47 | year = 2003 | pmid = 14683519 | doi = 10.2174/1568026033451709 }}
38. ^1 2 {{cite journal | vauthors = Novac N, Heinzel T | title = Nuclear receptors: overview and classification | journal = Current Drug Targets. Inflammation and Allergy | volume = 3 | issue = 4 | pages = 335–46 | date = December 2004 | pmid = 15584884 | doi = 10.2174/1568010042634541 | url = http://www.ingentaconnect.com/content/ben/cdtia/2004/00000003/00000004/art00002 }}
39. ^1 2 3 {{cite journal | title = A unified nomenclature system for the nuclear receptor superfamily | journal = Cell | volume = 97 | issue = 2 | pages = 161–3 | date = April 1999 | pmid = 10219237 | doi = 10.1016/S0092-8674(00)80726-6 | author1 = Nuclear Receptors Nomenclature Committee }}
40. ^1 {{cite journal | vauthors = Olefsky JM | title = Nuclear receptor minireview series | journal = The Journal of Biological Chemistry | volume = 276 | issue = 40 | pages = 36863–4 | date = October 2001 | pmid = 11459855 | doi = 10.1074/jbc.R100047200 }}
41. ^1 {{cite journal | vauthors = Overington JP, Al-Lazikani B, Hopkins AL | title = How many drug targets are there? | journal = Nature Reviews. Drug Discovery | volume = 5 | issue = 12 | pages = 993–6 | date = December 2006 | pmid = 17139284 | doi = 10.1038/nrd2199 }}
42. ^1 {{cite journal | vauthors = Pascual G, Glass CK | title = Nuclear receptors versus inflammation: mechanisms of transrepression | journal = Trends in Endocrinology and Metabolism | volume = 17 | issue = 8 | pages = 321–7 | date = October 2006 | pmid = 16942889 | doi = 10.1016/j.tem.2006.08.005 }}
43. ^1 {{cite journal | vauthors = Reitzel AM, Pang K, Ryan JF, Mullikin JC, Martindale MQ, Baxevanis AD, Tarrant AM | title = Nuclear receptors from the ctenophore Mnemiopsis leidyi lack a zinc-finger DNA-binding domain: lineage-specific loss or ancestral condition in the emergence of the nuclear receptor superfamily? | journal = EvoDevo | volume = 2 | issue = 1 | pages = 3 | date = February 2011 | pmid = 21291545 | pmc = 3038971 | doi = 10.1186/2041-9139-2-3 }}
44. ^1 {{PDB|2C7A}}; {{cite journal | vauthors = Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME | title = Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements | journal = Molecular Endocrinology | volume = 20 | issue = 12 | pages = 3042–52 | date = December 2006 | pmid = 16931575 | pmc = 2532839 | doi = 10.1210/me.2005-0511 }}
45. ^1 {{cite journal | vauthors = Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL | title = The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen | journal = Cell | volume = 95 | issue = 7 | pages = 927–37 | date = December 1998 | pmid = 9875847 | doi = 10.1016/S0092-8674(00)81717-1 }}
46. ^1 {{cite journal | vauthors = Sluder AE, Maina CV | title = Nuclear receptors in nematodes: themes and variations | journal = Trends in Genetics | volume = 17 | issue = 4 | pages = 206–13 | date = April 2001 | pmid = 11275326 | doi = 10.1016/S0168-9525(01)02242-9 }}
47. ^1 {{cite journal | vauthors = Smith CL, O'Malley BW | title = Coregulator function: a key to understanding tissue specificity of selective receptor modulators | journal = Endocrine Reviews | volume = 25 | issue = 1 | pages = 45–71 | date = February 2004 | pmid = 14769827 | doi = 10.1210/er.2003-0023 }}
48. ^1 {{cite journal | vauthors = Storey NM, O'Bryan JP, Armstrong DL | title = Rac and Rho mediate opposing hormonal regulation of the ether-a-go-go-related potassium channel | journal = Current Biology | volume = 12 | issue = 1 | pages = 27–33 | date = January 2002 | pmid = 11790300 | doi = 10.1016/S0960-9822(01)00625-X }}
49. ^1 {{cite journal | vauthors = Storey NM, Gentile S, Ullah H, Russo A, Muessel M, Erxleben C, Armstrong DL | title = Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 13 | pages = 5197–201 | date = March 2006 | pmid = 16549781 | pmc = 1458817 | doi = 10.1073/pnas.0600089103 }}
50. ^1 {{cite journal | vauthors = Tata JR | title = One hundred years of hormones | journal = EMBO Reports | volume = 6 | issue = 6 | pages = 490–6 | date = June 2005 | pmid = 15940278 | pmc = 1369102 | doi = 10.1038/sj.embor.7400444 }}
51. ^1 2 {{cite journal | vauthors = Wärnmark A, Treuter E, Wright AP, Gustafsson JA | title = Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation | journal = Molecular Endocrinology | volume = 17 | issue = 10 | pages = 1901–9 | date = October 2003 | pmid = 12893880 | doi = 10.1210/me.2002-0384 }}
52. ^1 {{cite journal | vauthors = Weatherman RV, Fletterick RJ, Scanlan TS | title = Nuclear-receptor ligands and ligand-binding domains | journal = Annual Review of Biochemistry | volume = 68 | issue = | pages = 559–81 | year = 1999 | pmid = 10872460 | doi = 10.1146/annurev.biochem.68.1.559 }}
53. ^1 {{cite journal | vauthors = Wu W, Niles EG, El-Sayed N, Berriman M, LoVerde PT | title = Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: sixteen new members and a novel subfamily | journal = Gene | volume = 366 | issue = 2 | pages = 303–15 | date = February 2006 | pmid = 16406405 | doi = 10.1016/j.gene.2005.09.013 }}
54. ^1 {{cite journal | vauthors = Wu W, Niles EG, Hirai H, LoVerde PT | title = Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domains | journal = BMC Evolutionary Biology | volume = 7 | pages = 27 | date = February 2007 | pmid = 17319953 | pmc = 1810520 | doi = 10.1186/1471-2148-7-27 }}
55. ^1 2 {{cite journal | vauthors = Zhang Z, Burch PE, Cooney AJ, Lanz RB, Pereira FA, Wu J, Gibbs RA, Weinstock G, Wheeler DA | title = Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome | journal = Genome Research | volume = 14 | issue = 4 | pages = 580–90 | date = April 2004 | pmid = 15059999 | pmc = 383302 | doi = 10.1101/gr.2160004 }}
56. ^1 {{cite journal | vauthors = Zivadinovic D, Gametchu B, Watson CS | title = Membrane estrogen receptor-alpha levels in MCF-7 breast cancer cells predict cAMP and proliferation responses | journal = Breast Cancer Research | volume = 7 | issue = 1 | pages = R101–12 | year = 2005 | pmid = 15642158 | pmc = 1064104 | doi = 10.1186/bcr958 }}
[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]
}}

External links

  • {{MeshName|Nuclear+Receptors}}
  • {{cite web | url = http://www.iuphar-db.org/index_nh.jsp | title = The IUPHAR Compendium of the Pharmacology and Classification of the Nuclear Receptor Superfamily 2006E | accessdate = 2008-02-21 | author = Vincent Laudet | date = 2006 | format = | work = Nuclear Receptor Compendium | publisher = The International Union of Basic and Clinical Pharmacology | pages = | quote = }}
  • {{cite web | url = http://www.nuclear-receptor.com | title = Nuclear Receptor online journal | accessdate = 2008-02-21 | date = | format = | work = Home page | publisher = published by BioMed Central (no longer accepting submissions since May 2007) | pages = | quote = }}
  • {{cite web| url =http://nrr.georgetown.edu/NRR/nrrhome.htm| title =Nuclear Receptor Resource| accessdate =2008-02-21| date =| website =| publisher =Georgetown University| pages =| archiveurl =https://web.archive.org/web/20080511195543/http://nrr.georgetown.edu/NRR/nrrhome.htm| archivedate =2008-05-11| quote =| deadurl =yes| df =}}
  • {{cite web | url = http://www.nursa.org/ | title = Nuclear Receptor Signaling Atlas (Receptors, Coactivators, Corepressors and Ligands) | accessdate = 2008-02-21 | date = | format = | website = | publisher = The NURSA Consortium | pages = | quote = an NIH-funded research consortium and database; includes open-access PubMed-indexed journal, Nuclear Receptor Signaling }}
  • {{cite web | url = http://www.nrresource.org/ | title = Nuclear Receptor Resource | accessdate = 2009-09-21 | date = | format = | website = | publisher = Jack Vanden Heuvel | pages = | quote = }}
{{Transcription factors|g2|state=collapsed}}{{Nuclear receptor ligands}}

3 : Intracellular receptors|Protein families|Transcription factors
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/12 6:44:41