Estrogen-related receptor: Difference between revisions

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* [[estrogen-related receptor gamma|ERRγ]] ({{gene|ESRRG}})
* [[estrogen-related receptor gamma|ERRγ]] ({{gene|ESRRG}})


ERRs bind enhancers throughout the genome where they exert effects on gene regulation. The ERR family exhibit varying transcriptional activation capabilities and physically interact with the transcriptional co-activators [[PPARGC1A|PGC1-alpha]] and PGC1-beta,<ref name=":0">{{cite journal | vauthors = Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A | title = The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 17 | pages = 6472–7 | date = April 2004 | pmid = 15087503 | doi = 10.1073/pnas.0308686101 | pmc = 404069 }}</ref><ref name=":1">{{cite journal | vauthors = Sonoda J, Laganière J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, Lee CH, Giguère V, Evans RM | title = Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense | journal = Genes & Development | volume = 21 | issue = 15 | pages = 1909–20 | date = August 2007 | pmid = 17671090 | pmc = 1935029 | doi = 10.1101/gad.1553007 }}</ref><ref>{{cite journal | vauthors = Huss JM, Kopp RP, Kelly DP | title = Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha | journal = The Journal of Biological Chemistry | volume = 277 | issue = 43 | pages = 40265–74 | date = October 2002 | pmid = 12181319 | doi = 10.1074/jbc.M206324200 }}</ref><ref>{{cite journal | vauthors = Laganière J, Tremblay GB, Dufour CR, Giroux S, Rousseau F, Giguère V | title = A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator-activated receptor gamma coactivator-1alpha control of ERRalpha expression | journal = The Journal of Biological Chemistry | volume = 279 | issue = 18 | pages = 18504–10 | date = April 2004 | pmid = 14978033 | doi = 10.1074/jbc.M313543200 }}</ref><ref>{{cite journal | vauthors = Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A | title = The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) | journal = The Journal of Biological Chemistry | volume = 278 | issue = 11 | pages = 9013–8 | date = March 2003 | pmid = 12522104 | doi = 10.1074/jbc.M212923200 }}</ref> via their AF-2 domains and the leucine-rich nuclear receptor interacting motifs (LxxLL) present in the PGC-1 proteins,<ref name=":2">{{cite journal | vauthors = Giguère V | title = Transcriptional control of energy homeostasis by the estrogen-related receptors | journal = Endocrine Reviews | volume = 29 | issue = 6 | pages = 677–96 | date = October 2008 | pmid = 18664618 | doi = 10.1210/er.2008-0017 | url = https://doi.org/10.1210/er.2008-0017 }}</ref> The ERR family have been demonstrated to control energy homeostasis,<ref name=":2" /><ref>{{cite journal | vauthors = Sladek R, Bader JA, Giguère V | title = The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene | journal = Molecular and Cellular Biology | volume = 17 | issue = 9 | pages = 5400–9 | date = September 1997 | pmid = 9271417 }}</ref> oxidative metabolism,<ref name=":0" /><ref>{{cite journal | vauthors = Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM | title = Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 17 | pages = 6570–5 | date = April 2004 | pmid = 15100410 | doi = 10.1073/pnas.0401401101 | pmc = 404086 }}</ref> and mitochondrial biogenesis,<ref name=":0" /> while effecting mammalian physiology in the heart,<ref>{{cite journal | vauthors = Huss JM, Imahashi K, Dufour CR, Weinheimer CJ, Courtois M, Kovacs A, Giguère V, Murphy E, Kelly DP | title = The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload | journal = Cell Metabolism | volume = 6 | issue = 1 | pages = 25–37 | date = July 2007 | pmid = 17618854 | doi = 10.1016/j.cmet.2007.06.005 }}</ref><ref>{{cite journal | vauthors = Alaynick WA, Kondo RP, Xie W, He W, Dufour CR, Downes M, Jonker JW, Giles W, Naviaux RK, Giguère V, Evans RM | title = ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart | journal = Cell Metabolism | volume = 6 | issue = 1 | pages = 13–24 | date = July 2007 | pmid = 17618853 | doi = 10.1016/j.cmet.2007.06.007 }}</ref><ref>{{cite journal | vauthors = Wang T, McDonald C, Petrenko NB, Leblanc M, Wang T, Giguere V, Evans RM, Patel VV, Pei L | title = Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function | journal = Molecular and Cellular Biology | volume = 35 | issue = 7 | pages = 1281–98 | date = April 2015 | pmid = 25624346 | pmc = 4355525 | doi = 10.1128/MCB.01156-14 }}</ref><ref>{{cite journal | vauthors = Dufour CR, Wilson BJ, Huss JM, Kelly DP, Alaynick WA, Downes M, Evans RM, Blanchette M, Giguère V | title = Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma | journal = Cell Metabolism | volume = 5 | issue = 5 | pages = 345–56 | date = May 2007 | pmid = 17488637 | doi = 10.1016/j.cmet.2007.03.007 }}</ref> brown adipose tissue,<ref>{{cite journal | vauthors = Villena JA, Hock MB, Chang WY, Barcas JE, Giguère V, Kralli A | title = Orphan nuclear receptor estrogen-related receptor alpha is essential for adaptive thermogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 4 | pages = 1418–23 | date = January 2007 | pmid = 17229846 | pmc = 1783094 | doi = 10.1073/pnas.0607696104 }}</ref><ref>{{cite journal | vauthors = Emmett MJ, Lim HW, Jager J, Richter HJ, Adlanmerini M, Peed LC, Briggs ER, Steger DJ, Ma T, Sims CA, Baur JA, Pei L, Won KJ, Seale P, Gerhart-Hines Z, Lazar MA | title = Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge | journal = Nature | volume = 546 | issue = 7659 | pages = 544–548 | date = June 2017 | pmid = 28614293 | doi = 10.1038/nature22819 | via =  }}</ref><ref>{{cite journal | vauthors = Dixen K, Basse AL, Murholm M, Isidor MS, Hansen LH, Petersen MC, Madsen L, Petrovic N, Nedergaard J, Quistorff B, Hansen JB | title = ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes | journal = Obesity | volume = 21 | issue = 3 | pages = 516–24 | date = March 2013 | pmid = 23404793 | doi = 10.1002/oby.20067 }}</ref> white adipose tissue,<ref>{{cite journal | vauthors = Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguère V | title = Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha | journal = Molecular and Cellular Biology | volume = 23 | issue = 22 | pages = 7947–56 | date = November 2003 | pmid = 14585956 | doi = 10.1128/MCB.23.22.7947-7956.2003 | pmc = 262360 }}</ref> placenta,<ref>{{cite journal | vauthors = Luo J, Sladek R, Bader JA, Matthyssen A, Rossant J, Giguère V | title = Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta | journal = Nature | volume = 388 | issue = 6644 | pages = 778–82 | date = August 1997 | pmid = 9285590 | doi = 10.1038/42022 }}</ref> macrophages,<ref name=":1" /> and demonstrated additional roles in diabetes and [[cancer]].<ref name="ariazi2">{{cite journal | vauthors = Ariazi EA, Jordan VC | title = Estrogen-related receptors as emerging targets in cancer and metabolic disorders | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 3 | pages = 203–15 | year = 2006 | pmid = 16515477 | doi = 10.2174/156802606776173483 }}</ref> The contributions of individual ERRs to physiology continue to be elucidated through the generation of sophisticated tissue-specific gene knockout mouse models.


ERRs bind to estrogen response elements and modulate [[Transcription (genetics)|transcription]] but are not activated by estrogens.
== References ==
They also have their own response elements: ERREs. ERRs have been associated with energy homeostasis, diabetes and [[cancer]].<ref name="ariazi">{{cite journal |author=Ariazi E, Jordan V |title=Estrogen-related receptors as emerging targets in cancer and metabolic disorders |journal=Curr Top Med Chem |volume=6 |issue=3 |pages=203–15 |year=2006 |pmid=16515477 |doi=10.2174/156802606776173483}}</ref>
 
==References==
{{Reflist}}
{{Reflist}}


==External links==
== External links ==
* {{MeshName|ERRalpha+estrogen-related+receptor}}
* {{MeshName|ERRalpha+estrogen-related+receptor}}
* {{MeshName|estrogen+receptor-related+receptor+beta}}
* {{MeshName|estrogen+receptor-related+receptor+beta}}
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{{gene-14-stub}}
{{gene-14-stub}}


{{Transcription factors|g2}}
{{Transcription factors|g2}}

Revision as of 13:20, 5 June 2018

estrogen-related receptor alpha
Identifiers
SymbolESRRA
Alt. symbolsESRL1
Entrez2101
HUGO3471
OMIM601998
RefSeqNM_004451
UniProtP11474
Other data
LocusChr. 11 q12
estrogen-related receptor beta
Identifiers
SymbolESRRB
Alt. symbolsESRL2
Entrez2103
HUGO3473
OMIM602167
RefSeqNM_004452
UniProtO95718
Other data
LocusChr. 14 q24.3
estrogen-related receptor gamma
Identifiers
SymbolESRRG
Entrez2104
HUGO3474
OMIM602969
RefSeqNM_206595
UniProtP62508
Other data
LocusChr. 1 q41

The ERRs are orphan nuclear receptors, meaning the identity of their endogenous ligand has yet to be unambiguously determined. They are named because of sequence homology with estrogen receptors, but do not appear to bind estrogens or other tested steroid hormones.

There are three human estrogen related receptors:

ERRs bind enhancers throughout the genome where they exert effects on gene regulation. The ERR family exhibit varying transcriptional activation capabilities and physically interact with the transcriptional co-activators PGC1-alpha and PGC1-beta,[1][2][3][4][5] via their AF-2 domains and the leucine-rich nuclear receptor interacting motifs (LxxLL) present in the PGC-1 proteins,[6] The ERR family have been demonstrated to control energy homeostasis,[6][7] oxidative metabolism,[1][8] and mitochondrial biogenesis,[1] while effecting mammalian physiology in the heart,[9][10][11][12] brown adipose tissue,[13][14][15] white adipose tissue,[16] placenta,[17] macrophages,[2] and demonstrated additional roles in diabetes and cancer.[18] The contributions of individual ERRs to physiology continue to be elucidated through the generation of sophisticated tissue-specific gene knockout mouse models.

References

  1. ↑ 1.0 1.1 1.2 Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A (April 2004). "The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 101 (17): 6472–7. doi:10.1073/pnas.0308686101. PMC 404069. PMID 15087503.
  2. ↑ 2.0 2.1 Sonoda J, Laganière J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, Lee CH, Giguère V, Evans RM (August 2007). "Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense". Genes & Development. 21 (15): 1909–20. doi:10.1101/gad.1553007. PMC 1935029. PMID 17671090.
  3. ↑ Huss JM, Kopp RP, Kelly DP (October 2002). "Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha". The Journal of Biological Chemistry. 277 (43): 40265–74. doi:10.1074/jbc.M206324200. PMID 12181319.
  4. ↑ Laganière J, Tremblay GB, Dufour CR, Giroux S, Rousseau F, Giguère V (April 2004). "A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator-activated receptor gamma coactivator-1alpha control of ERRalpha expression". The Journal of Biological Chemistry. 279 (18): 18504–10. doi:10.1074/jbc.M313543200. PMID 14978033.
  5. ↑ Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (March 2003). "The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha)". The Journal of Biological Chemistry. 278 (11): 9013–8. doi:10.1074/jbc.M212923200. PMID 12522104.
  6. ↑ 6.0 6.1 Giguère V (October 2008). "Transcriptional control of energy homeostasis by the estrogen-related receptors". Endocrine Reviews. 29 (6): 677–96. doi:10.1210/er.2008-0017. PMID 18664618.
  7. ↑ Sladek R, Bader JA, Giguère V (September 1997). "The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene". Molecular and Cellular Biology. 17 (9): 5400–9. PMID 9271417.
  8. ↑ Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM (April 2004). "Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle". Proceedings of the National Academy of Sciences of the United States of America. 101 (17): 6570–5. doi:10.1073/pnas.0401401101. PMC 404086. PMID 15100410.
  9. ↑ Huss JM, Imahashi K, Dufour CR, Weinheimer CJ, Courtois M, Kovacs A, Giguère V, Murphy E, Kelly DP (July 2007). "The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload". Cell Metabolism. 6 (1): 25–37. doi:10.1016/j.cmet.2007.06.005. PMID 17618854.
  10. ↑ Alaynick WA, Kondo RP, Xie W, He W, Dufour CR, Downes M, Jonker JW, Giles W, Naviaux RK, Giguère V, Evans RM (July 2007). "ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart". Cell Metabolism. 6 (1): 13–24. doi:10.1016/j.cmet.2007.06.007. PMID 17618853.
  11. ↑ Wang T, McDonald C, Petrenko NB, Leblanc M, Wang T, Giguere V, Evans RM, Patel VV, Pei L (April 2015). "Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function". Molecular and Cellular Biology. 35 (7): 1281–98. doi:10.1128/MCB.01156-14. PMC 4355525. PMID 25624346.
  12. ↑ Dufour CR, Wilson BJ, Huss JM, Kelly DP, Alaynick WA, Downes M, Evans RM, Blanchette M, Giguère V (May 2007). "Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma". Cell Metabolism. 5 (5): 345–56. doi:10.1016/j.cmet.2007.03.007. PMID 17488637.
  13. ↑ Villena JA, Hock MB, Chang WY, Barcas JE, Giguère V, Kralli A (January 2007). "Orphan nuclear receptor estrogen-related receptor alpha is essential for adaptive thermogenesis". Proceedings of the National Academy of Sciences of the United States of America. 104 (4): 1418–23. doi:10.1073/pnas.0607696104. PMC 1783094. PMID 17229846.
  14. ↑ Emmett MJ, Lim HW, Jager J, Richter HJ, Adlanmerini M, Peed LC, Briggs ER, Steger DJ, Ma T, Sims CA, Baur JA, Pei L, Won KJ, Seale P, Gerhart-Hines Z, Lazar MA (June 2017). "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge". Nature. 546 (7659): 544–548. doi:10.1038/nature22819. PMID 28614293.
  15. ↑ Dixen K, Basse AL, Murholm M, Isidor MS, Hansen LH, Petersen MC, Madsen L, Petrovic N, Nedergaard J, Quistorff B, Hansen JB (March 2013). "ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes". Obesity. 21 (3): 516–24. doi:10.1002/oby.20067. PMID 23404793.
  16. ↑ Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguère V (November 2003). "Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha". Molecular and Cellular Biology. 23 (22): 7947–56. doi:10.1128/MCB.23.22.7947-7956.2003. PMC 262360. PMID 14585956.
  17. ↑ Luo J, Sladek R, Bader JA, Matthyssen A, Rossant J, Giguère V (August 1997). "Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta". Nature. 388 (6644): 778–82. doi:10.1038/42022. PMID 9285590.
  18. ↑ Ariazi EA, Jordan VC (2006). "Estrogen-related receptors as emerging targets in cancer and metabolic disorders". Current Topics in Medicinal Chemistry. 6 (3): 203–15. doi:10.2174/156802606776173483. PMID 16515477.

External links

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