Os02g0100200 - Revision history

Xysj2012: /* Structured Information */

2015-05-14T05:17:11Z

‎Structured Information

Zhishp: /* Ligands */

2014-06-08T08:42:38Z

‎Ligands

Zhishp: /* Mechanism of action */

2014-06-08T08:05:42Z

‎Mechanism of action

Zhishp: /* References */

2014-06-08T08:03:45Z

‎References

Zhishp: /* Mechanism of action */

2014-06-08T07:53:32Z

‎Mechanism of action

Zhishp: /* Mechanism of action */

2014-06-08T07:51:32Z

‎Mechanism of action

Zhishp: /* Mechanism of action */

2014-06-08T07:48:49Z

‎Mechanism of action

Zhishp: /* Nuclear receptors */

2014-06-08T07:48:14Z

‎Nuclear receptors

Zhishp: /* Mechanism of action */

2014-06-08T07:47:05Z

‎Mechanism of action

Zhishp: /* Mechanism of action */

2014-06-08T07:46:17Z

‎Mechanism of action

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 ==Structured Information==
-  ORGANISM  Oryza sativa Japonica Group
 [[Category:Genes]]
 [[Category:Japonica mRNA]]

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 Steroid receptors of the nuclear receptor family are all transcription factors. Depending upon the type of receptor, they are either located in the cytosol and move to the cell nucleus upon activation, or remain in the nucleus waiting for the steroid hormone to enter and activate them. This uptake into the nucleus is facilitated by nuclear localization signal (NLS) found in the hinge region of the receptor. This region of the receptor is covered up by heat shock proteins (HSPs) which bind the receptor until the hormone is present. Upon binding by the hormone the receptor undergoes a conformational change releasing the HSP, and the receptor together with the bound hormone enter the nucleus to act upon transcription.
 ===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 are nuclear receptors.
 A number of nuclear receptors, referred to as orphan receptors, 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.
 ===Expression===

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 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. 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]
+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. 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.<ref name="ref5"/>
+Accordingly, nuclear receptors may be subdivided into the following four mechanistic classes:<ref name="ref5"/><ref name="ref6"/>
 Type I
@@ Line 80: / Line 79: @@
 [[File:800px-Nuclear_receptor_action.png|200px|thumb|left|alt text]]
-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.[22]
+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.<ref name="ref7"/>
 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 still unknown.
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 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. 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.
-nuclear receptors include principally subfamily 1, for example the retinoic acid receptor, retinoid X receptor and thyroid hormone receptor.[23]
+nuclear receptors include principally subfamily 1, for example the retinoic acid receptor, retinoid X receptor and thyroid hormone receptor.<ref name="ref8"/>
 Type III

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 <ref name="ref3">Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E (August 2004). "Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens". Steroids 69 (8–9): 553–9. doi:10.1016/j.steroids.2004.05.013. PMID 15288769.</ref>
 <ref name="ref4">Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, Rago V, Andò S (March 2004). "Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway". J. Clin. Endocrinol. Metab. 89 (3): 1443–51. doi:10.1210/jc.2003-031681. PMID 15001646.</ref>
 </references>

← Older revision		Revision as of 07:53, 8 June 2014
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	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. 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 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. 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.[23]		nuclear receptors include principally subfamily 1, for example the retinoic acid receptor, retinoid X receptor and thyroid hormone receptor.[23]

← Older revision		Revision as of 07:51, 8 June 2014
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	Type II		Type II
		+
		+	[[File:800px-Type_ii_nuclear_receptor_action.png\|200px\|thumb\|left\|alt text]]

	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. 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 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. 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.

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 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.[22]
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 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

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 Subfamily 3: Estrogen Receptor-like
 Group A: Estrogen receptor (Sex hormones: Estrogen)
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 : Androgen receptor (AR; NR3C4, AR) (Sex hormones: Testosterone)
 ====Mechanism of action====

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 Accordingly, nuclear receptors may be subdivided into the following four mechanistic classes:[4][5]
-Type I[edit]
+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.[22]
@@ Line 83: / Line 84: @@
 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[edit]
+[[800px-Nuclear_receptor_action.png|200px|thumb|left|alt text]]
 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. 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.[23]
+Type II
 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[edit]
+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.