JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on November 26, 2004
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
279/48/50050    most recent
M407309200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Garside, H. J.
Right arrow Articles by Ray, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garside, H. J.
Right arrow Articles by Ray, D. W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print September 8, 2004
J. Biol. Chem, 10.1074/jbc.M407309200
Submitted on June 30, 2004
Revised on September 7, 2004
Accepted on September 8, 2004

Glucocorticoid ligands specify different interactions with NF-kB by allosteric effects on the glucocorticoid receptor DNA binding domain

Helen J. Garside, Adam Stevens, Stuart Farrow, Claire Normand, Benoit Houle, Andy Berry, Barbara Maschera, and David W. Ray

Centre for Molecular Medicine, University of Manchester, Manchester M13 9PT

Corresponding Author: David.W.Ray{at}man.ac.uk

Glucocorticoids inhibit inflammation by acting through the glucocorticoid receptor (GR) and powerfully repressing Nuclear Factor -kB (NF-kB) function. Ligand binding to the C-terminal of GR promotes the nuclear translocation of the receptor and binding to NF-kB through the GR DNA binding domain. We sought how ligand recognition influences the interaction between NF-kB and GR Both dexamethasone (agonist), and RU486 (antagonist) promote efficient nuclear translocation, and we show occupancy of the same intranuclear compartment as NF-kB with both ligands. However, unlike dexamethasone, RU486 had negligible activity to inhibit NF-kB transactivation. This failure may stem from altered co-factor recruitment, or altered interaction with NF-kB. Using both GST pull-down and Bioluminescence Resonance Energy Transfer (BRET) approaches we identified a major glucocorticoid ligand effect on interaction between the GR and the p65 component of NF-kB, with RU486 inhibiting recruitment compared to dexamethasone. Using the BRET assay, we found that RU486 efficiently recruited NCoR to the GR, unlike dexamethasone, which recruited SRC1. Therefore RU486 promotes differential protein recruitment to both the C terminal and DNA binding domain of the receptor. Importantly using chromatin immunoprecipitation we show that impaired interaction between GR and p65 with RU486 leads to reduced recruitment of the GR to the NF-kB responsive region of the IL-8 promoter, again in contrast to dexamethasone that significantly increased GR binding. We demonstrate that ligand-induced conformation of the GR C-terminal has profound effects on the functional surface generated by the DNA binding domain of the GR. This has implications for understanding ligand-dependent interdomain communication.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J EndocrinolHome page
L. Rice, C. E Waters, J. Eccles, H. Garside, P. Sommer, P. Kay, F. H Blackhall, L. Zeef, B. Telfer, I. Stratford, et al.
Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
J. Endocrinol., September 1, 2008; 198(3): 499 - 509.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Yemelyanov, J. Czwornog, L. Gera, S. Joshi, R. T. Chatterton Jr., and I. Budunova
Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells
Cancer Res., June 15, 2008; 68(12): 4763 - 4773.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
L. Matthews, A. Berry, V. Ohanian, J. Ohanian, H. Garside, and D. Ray
Caveolin Mediates Rapid Glucocorticoid Effects and Couples Glucocorticoid Action to the Antiproliferative Program
Mol. Endocrinol., June 1, 2008; 22(6): 1320 - 1330.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
P. K. Bhavsar, M. B. Sukkar, N. Khorasani, K.-Y. Lee, and K. F. Chung
Glucocorticoid suppression of CX3CL1 (fractalkine) by reduced gene promoter recruitment of NF-{kappa}B
FASEB J, June 1, 2008; 22(6): 1807 - 1816.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
A McMaster, T Chambers, Q-J Meng, S Grundy, A S I Loudon, R Donn, and D W Ray
Real-time analysis of gene regulation by glucocorticoid hormones
J. Endocrinol., May 1, 2008; 197(2): 205 - 211.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. P. Fitzsimons, S. Ahmed, C. F. W. Wittevrongel, T. G. Schouten, T. F. Dijkmans, W. J. J. M. Scheenen, M. J. M. Schaaf, E. Ronald de Kloet, and E. Vreugdenhil
The Microtubule-Associated Protein Doublecortin-Like Regulates the Transport of the Glucocorticoid Receptor in Neuronal Progenitor Cells
Mol. Endocrinol., February 1, 2008; 22(2): 248 - 262.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Kratzner, F. Frohlich, K. Lepler, M. Schroder, K. Roher, C. Dickel, M. V. Tzvetkov, T. Quentin, E. Oetjen, and W. Knepel
A Peroxisome Proliferator-Activated Receptor {gamma}-Retinoid X Receptor Heterodimer Physically Interacts with the Transcriptional Activator PAX6 to Inhibit Glucagon Gene Transcription
Mol. Pharmacol., February 1, 2008; 73(2): 509 - 517.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Newton and N. S. Holden
Separating Transrepression and Transactivation: A Distressing Divorce for the Glucocorticoid Receptor?
Mol. Pharmacol., October 1, 2007; 72(4): 799 - 809.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. Neumann and M. Naumann
Beyond I{kappa}Bs: alternative regulation of NF-{kappa}B activity
FASEB J, September 1, 2007; 21(11): 2642 - 2654.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
A. McMaster and D. W. Ray
Modelling the glucocorticoid receptor and producing therapeutic agents with anti-inflammatory effects but reduced side-effects
Exp Physiol, March 1, 2007; 92(2): 299 - 309.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. Donn, A. Berry, A. Stevens, S. Farrow, J. Betts, R. Stevens, C. Clayton, J. Wang, L. Warnock, J. Worthington, et al.
Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII
FASEB J, February 1, 2007; 21(2): 402 - 414.
[Abstract] [Full Text] [PDF]

Home page
 Adv. Physiol. Educ.Home page
E. Dale, M. Davis, and D. L. Faustman
A role for transcription factor NF-{kappa}B in autoimmunity: possible interactions of genes, sex, and the immune response
Advan Physiol Educ, December 1, 2006; 30(4): 152 - 158.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. E. Chivers, W. Gong, E. M. King, J. Seybold, J. C. Mak, L. E. Donnelly, N. S. Holden, and R. Newton
Analysis of the Dissociated Steroid RU24858 Does Not Exclude a Role for Inducible Genes in the Anti-Inflammatory Actions of Glucocorticoids
Mol. Pharmacol., December 1, 2006; 70(6): 2084 - 2095.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
H. Garside, C. Waters, A. Berry, L. Rice, H. C Ardley, A. White, P. A Robinson, and D. Ray
UbcH7 interacts with the glucocorticoid receptor and mediates receptor autoregulation.
J. Endocrinol., September 1, 2006; 190(3): 621 - 629.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Tahera, I. Meltser, P. Johansson, A. C. Hansson, and B. Canlon
Glucocorticoid Receptor and Nuclear Factor-{kappa}B Interactions in Restraint Stress-Mediated Protection against Acoustic Trauma
Endocrinology, September 1, 2006; 147(9): 4430 - 4437.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. M. Schaaf, L. Willetts, B. P. Hayes, B. Maschera, E. Stylianou, and S. N. Farrow
The Relationship between Intranuclear Mobility of the NF-{kappa}B Subunit p65 and Its DNA Binding Affinity
J. Biol. Chem., August 4, 2006; 281(31): 22409 - 22420.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Friedrichsen, C. V. Harper, S. Semprini, M. Wilding, A. D. Adamson, D. G. Spiller, G. Nelson, J. J. Mullins, M. R. H. White, and J. R. E. Davis
Tumor Necrosis Factor-{alpha} Activates the Human Prolactin Gene Promoter via Nuclear Factor-{kappa}B Signaling
Endocrinology, February 1, 2006; 147(2): 773 - 781.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
T. M Lindstrom and P. R Bennett
The role of nuclear factor kappa B in human labour
Reproduction, November 1, 2005; 130(5): 569 - 581.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
T. Rhen and J. A. Cidlowski
Antiinflammatory action of glucocorticoids--new mechanisms for old drugs.
N. Engl. J. Med., October 20, 2005; 353(16): 1711 - 1723.
[Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Yoshikawa, K. Yamamoto, N. Shimizu, S. Yamada, C. Morimoto, and H. Tanaka
The Distinct Agonistic Properties of the Phenylpyrazolosteroid Cortivazol Reveal Interdomain Communication within the Glucocorticoid Receptor
Mol. Endocrinol., May 1, 2005; 19(5): 1110 - 1124.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.