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(Redirected from Estrogen related receptor)
estrogen-related receptor alpha
Identifiers
Symbol ESRRA
Alt. symbolsESRL1
NCBI gene 2101
HGNC 3471
OMIM 601998
RefSeq NM_004451
UniProt P11474
Other data
Locus Chr. 11 q12
Search for
Structures Swiss-model
Domains InterPro
estrogen-related receptor beta
Identifiers
Symbol ESRRB
Alt. symbolsESRL2
NCBI gene 2103
HGNC 3473
OMIM 602167
RefSeq NM_004452
UniProt O95718
Other data
Locus Chr. 14 q24.3
Search for
Structures Swiss-model
Domains InterPro
estrogen-related receptor gamma
Identifiers
Symbol ESRRG
NCBI gene 2104
HGNC 3474
OMIM 602969
RefSeq NM_206595
UniProt P62508
Other data
Locus Chr. 1 q41
Search for
Structures Swiss-model
Domains InterPro

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.[ citation needed]

References

  1. ^ a b c 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. Bibcode: 2004PNAS..101.6472S. doi: 10.1073/pnas.0308686101. PMC  404069. PMID  15087503.
  2. ^ a b 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. ^ a b 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. doi: 10.1128/mcb.17.9.5400. PMC  232390. 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. Bibcode: 2004PNAS..101.6570M. 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. Bibcode: 2007PNAS..104.1418V. 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. Bibcode: 2017Natur.546..544E. doi: 10.1038/nature22819. PMC  5826652. 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. S2CID  206317418.
  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. Bibcode: 1997Natur.388..778L. doi: 10.1038/42022. PMID  9285590. S2CID  4371787.
  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