The effect of Glucocorticoids on target gene expression (Rattus norvegicus)

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Nucleus2462424242410, 1513, 14, 229, 1982424CellREInhibiting EffectsPromoterTarget GeneGRERecyclingMAP kinase pathwaycytokinesCOX-2GITRlipid mediatorsbeta2 adrenergic receptorphospholipase A2p59Anti-Inflammatory Proteins3, 172, 4, 64, 6, 12, 2016, 25Glucocorticoid ReceptorGlucocorticoidsHsp70RrasGlucocorticoid Receptor24Hsp90aa118Hsp90ab118Glucocorticoid ReceptorGlucocorticoidsRrasHsp70p59Hsp90aa1Hsp90ab1Glucocorticoid ReceptorRrasHsp70p59Hsp90aa1Hsp90ab1GlucocorticoidsGlucocorticoid ReceptorGlucocorticoids24Nf-kB, etcGlucocorticoid ReceptorGlucocorticoidsNf-kB, etcchemokinesadhesion molecules4, 6, 12, 20mediator-synthesizing enzymes4, 6, 12, 204, 6Activating EffectsIkB-alphaDNA unwindinglipocortin-11, 11, 21, 2326GILZNf-kB5, 75, 7


This pathway provides a clear view of the effects of Glucocorticoids on target gene expression when binding to the GR (glucocorticoid receptor). Inhibiting and activiting effects are given as a result of target gene activation.

It summarizes the article of Pelaia et al, 2002, which explains the pathway very detailed.

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  1. Ayer DE; ''Histone deacetylases: transcriptional repression with SINers and NuRDs.''; Trends Cell Biol, 1999 PubMed Europe PMC Scholia
  2. Barnes PJ, Pedersen S, Busse WW; ''Efficacy and safety of inhaled corticosteroids. New developments.''; Am J Respir Crit Care Med, 1998 PubMed Europe PMC Scholia
  3. Barnes PJ; ''Cytokine modulators as novel therapies for asthma.''; Annu Rev Pharmacol Toxicol, 2002 PubMed Europe PMC Scholia
  4. Umland SP, Schleimer RP, Johnston SL; ''Review of the molecular and cellular mechanisms of action of glucocorticoids for use in asthma.''; Pulm Pharmacol Ther, 2002 PubMed Europe PMC Scholia
  5. Ayroldi E, Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C; ''Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB.''; Blood, 2001 PubMed Europe PMC Scholia
  6. Adcock IM, Ito K; ''Molecular mechanisms of corticosteroid actions.''; Monaldi Arch Chest Dis, 2000 PubMed Europe PMC Scholia
  7. Riccardi C, Cifone MG, Migliorati G; ''Glucocorticoid hormone-induced modulation of gene expression and regulation of T-cell death: role of GITR and GILZ, two dexamethasone-induced genes.''; Cell Death Differ, 1999 PubMed Europe PMC Scholia
  8. Bertorelli G, Bocchino V, Olivieri D; ''Heat shock protein interactions with the glucocorticoid receptor.''; Pulm Pharmacol Ther, 1998 PubMed Europe PMC Scholia
  9. McKay LI, Cidlowski JA; ''Molecular control of immune/inflammatory responses: interactions between nuclear factor-kappa B and steroid receptor-signaling pathways.''; Endocr Rev, 1999 PubMed Europe PMC Scholia
  10. Mitchell PJ, Tjian R; ''Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins.''; Science, 1989 PubMed Europe PMC Scholia
  11. Nightingale KP, Wellinger RE, Sogo JM, Becker PB; ''Histone acetylation facilitates RNA polymerase II transcription of the Drosophila hsp26 gene in chromatin.''; EMBO J, 1998 PubMed Europe PMC Scholia
  12. Barnes PJ; ''Therapeutic strategies for allergic diseases.''; Nature, 1999 PubMed Europe PMC Scholia
  13. Winzen R, Kracht M, Ritter B, Wilhelm A, Chen CY, Shyu AB, Mueller M, Gaestel M, Resch K, Holtmann H; ''The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism.''; EMBO J, 1999 PubMed Europe PMC Scholia
  14. Newton R, Seybold J, Kuitert LM, Bergmann M, Barnes PJ; ''Repression of cyclooxygenase-2 and prostaglandin E2 release by dexamethasone occurs by transcriptional and post-transcriptional mechanisms involving loss of polyadenylated mRNA.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  15. Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB; ''Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA.''; Nature, 1991 PubMed Europe PMC Scholia
  16. Pelaia G, Marsico SA; ''Regulation of beta 2-adrenergic receptors and the implications for bronchial asthma: an update.''; Monaldi Arch Chest Dis, 1994 PubMed Europe PMC Scholia
  17. Dong C, Davis RJ, Flavell RA; ''MAP kinases in the immune response.''; Annu Rev Immunol, 2002 PubMed Europe PMC Scholia
  18. Smith DF, Toft DO; ''Steroid receptors and their associated proteins.''; Mol Endocrinol, 1993 PubMed Europe PMC Scholia
  19. Barnes PJ, Adcock IM; ''NF-kappa B: a pivotal role in asthma and a new target for therapy.''; Trends Pharmacol Sci, 1997 PubMed Europe PMC Scholia
  20. Pelaia G, Vatrella A, Calabrese C, Mazzarella G, Marsico SA; ''New perspectives in asthma treatment.''; Allergy, 2000 PubMed Europe PMC Scholia
  21. Ito K, Barnes PJ, Adcock IM; ''Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12.''; Mol Cell Biol, 2000 PubMed Europe PMC Scholia
  22. Bickel M, Cohen RB, Pluznik DH; ''Post-transcriptional regulation of granulocyte-macrophage colony-stimulating factor synthesis in murine T cells.''; J Immunol, 1990 PubMed Europe PMC Scholia
  23. Glass CK, Rosenfeld MG; ''The coregulator exchange in transcriptional functions of nuclear receptors.''; Genes Dev, 2000 PubMed Europe PMC Scholia
  24. Pelaia G, Vatrella A, Cuda G, Maselli R, Marsico SA; ''Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases.''; Life Sci, 2003 PubMed Europe PMC Scholia
  25. Barnes PJ; ''Beta-adrenergic receptors and their regulation.''; Am J Respir Crit Care Med, 1995 PubMed Europe PMC Scholia
  26. Flower RJ, Rothwell NJ; ''Lipocortin-1: cellular mechanisms and clinical relevance.''; Trends Pharmacol Sci, 1994 PubMed Europe PMC Scholia


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102081view19:39, 28 November 2018EgonwRemoved whitespace in PubMed identifiers.
82989view00:48, 17 November 2015Mkutmonfixed issue in references
82979view23:58, 16 November 2015Mkutmonfixed outdated identifiers
78467view10:27, 7 January 2015MaintBotadded missing graphIds
74090view11:46, 29 March 2014EgonwAdded ChEBI ids for 'glucocorticoids'.
67697view11:51, 26 June 2013DdiglesOntology Term : 'glucocorticoid signaling pathway' added !
58919view05:09, 21 February 2013MaintBotUpdated Ensembl data source
42205view21:09, 7 March 2011KhanspersModified categories
42204view21:09, 7 March 2011KhanspersFixed unconnected lines
41647view02:33, 2 March 2011MaintBotRemoved redundant pathway information and comments
40379view13:48, 23 February 2011RfijtenModified description
40378view13:47, 23 February 2011RfijtenModified description
40374view13:43, 23 February 2011Rfijten
40371view13:42, 23 February 2011Rfijten
40369view13:38, 23 February 2011RfijtenPeriodical save, work in progress
40364view13:27, 23 February 2011RfijtenPeriodical save, work in progress
40358view13:17, 23 February 2011RfijtenPeriodical save, work in progress
40353view13:07, 23 February 2011RfijtenPeriodical save, work in progress
40349view12:57, 23 February 2011RfijtenPeriodical save, work in progress
40345view12:47, 23 February 2011RfijtenPeriodical save, work in progress
40338view12:26, 23 February 2011RfijtenPeriodical save, work in progress
40331view12:06, 23 February 2011RfijtenPeriodical save, work in progress
40325view11:56, 23 February 2011RfijtenPeriodical save, work in progress
40321view11:46, 23 February 2011RfijtenPeriodical save, work in progress
40315view11:36, 23 February 2011RfijtenNew pathway

External references


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NameTypeDatabase referenceComment
Anti-Inflammatory ProteinsGeneProduct
COX-2GeneProductENSRNOG00000030371 (Ensembl)
DNA unwindingPathway
GILZGeneProductENSRNOG00000056135 (Ensembl)
GITRGeneProductENSRNOG00000022012 (Ensembl)
Glucocorticoid ReceptorGeneProduct24413 (Entrez Gene)
GlucocorticoidsMetaboliteCHEBI:24261 (ChEBI)
Hsp70GeneProductENSRNOG00000016596 (Ensembl)
Hsp90aa1GeneProductENSRNOG00000007219 (Ensembl)
Hsp90ab1GeneProductENSRNOG00000019834 (Ensembl)
IkB-alphaGeneProductENSRNOG00000007390 (Ensembl)
MAP kinase pathwayPathway
Nf-kB, etcGeneProductENSRNOG00000023258 (Ensembl)
Nf-kBGeneProductENSRNOG00000023258 (Ensembl)
RrasGeneProductENSRNOG00000037247 (Ensembl)
adhesion moleculesGeneProduct
beta2 adrenergic receptorGeneProductENSRNOG00000019217 (Ensembl)
lipid mediatorsGeneProduct
lipocortin-1GeneProductENSRNOG00000017469 (Ensembl)
mediator-synthesizing enzymesGeneProduct
p59GeneProduct260321 (Entrez Gene)
phospholipase A2GeneProductENSRNOG00000002657 (Ensembl)

Annotated Interactions

No annotated interactions

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