Nuclear Integration of Glucocorticoid Receptor and Nuclear Factor-κB Signaling by CREB-binding Protein and Steroid Receptor Coactivator-1
Open accessAbstract
The p65 (RelA) component of nuclear factor-kappaB (NF-kappaB) and the glucocorticoid receptor (GR) mutually repress each other's ability to activate transcription. Both of these transcriptional activators depend upon the coactivators CREB-binding protein (CBP) and steroid receptor coactivator-1 (SRC-1) for maximal activity. Here we show that increased levels of CBP relieves the inhibition of glucocorticoid-mediated repression of NF-kappaB activity and the NF-kappaB-mediated repression of GR activity. SRC-1 can relieve the NF-kappaB-mediated repression of GR activity. We propose that cross-talk between the p65 component of NF-kappaB and glucocorticoid receptors is due, at least in part, to nuclear competition for limiting amounts of the coactivators CBP and SRC-1, thus providing a novel mechanism for decreasing expression of genes involved in the inflammatory response.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GR and NF-κB compete with one another for the coactivators steroid receptor coactivator-1 (SRC-1) and CBP in the nucleus.
“GR and NF-κB have also been shown to compete with one another for the coactivators steroid receptor coactivator-1 (SRC-1) and CBP in the nucleus.68”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [68]
NF-κB-mediated repression of GR activity is inhibited by overexpression of CBP (and vice versa), and GR activity is also inhibited by SRC-1 over-expression.
“Indeed, NF-κB–mediated repression of GR activity is inhibited by overexpression of CBP (and vice versa), and GR activity is also inhibited by SRC-1 over-expression.68”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [68]
Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964 · see citing works
DNA binding of the glucocorticoid receptor is not essential for survival
Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81183-6 · Cited by 1,068 · see citing works
Scheinman, R. I., Gualberto, A., Jewell, C. M., Cidlowski, J. A., & Baldwin, A. S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.943 · Cited by 819 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0389 · Cited by 7,541 · see citing works
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750 · see citing works
Integrating cell-signalling pathways with NF-κB and IKK function
Perkins, N. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2083 · Cited by 2,350 · see citing works
Delerive, P., De Bosscher, K., Besnard, S., Vanden Berghe, W., Peters, J. M., Gonzalez, F. J., Fruchart, J.-C., Tedgui, A., Haegeman, G., & Staels, B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32048 · Cited by 1,089 · see citing works
How stress influences the immune response
Padgett, D. A., & Glaser, R. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00173-x · Cited by 1,059 · see citing works
De Bosscher, K., Vanden Berghe, W., & Haegeman, G. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0006 · Cited by 898 · see citing works
Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF‐κB
Chen, L., Mu, Y., & Greene, W. C. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf660 · Cited by 827 · see citing works
Denison, M. S., Soshilov, A. A., He, G., DeGroot, D. E., & Zhao, B. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr218 · Cited by 748 · see citing works
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.029 · Cited by 647 · see citing works
Self-citationPace, T. W. W., Hu, F., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.08.009 · Cited by 621 · see citing works
Glucocorticoid receptor control of transcription: precision and plasticity via allostery
Weikum, E. R., Knuesel, M. T., Ortlund, E. A., & Yamamoto, K. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.152 · Cited by 533 · see citing works
Mechanisms of glucocorticoid receptor signaling during inflammation
Smoak, K. A., & Cidlowski, J. A. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.06.010 · Cited by 420 · see citing works
Cytokines and Glucocorticoid Receptor Signaling
Pace, T. W. W., & Miller, A. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04984.x · Cited by 339 · see citing works
Beck, I. M. E., Vanden Berghe, W., Vermeulen, L., Yamamoto, K. R., Haegeman, G., & De Bosscher, K. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0013 · Cited by 298 · see citing works
Crosstalk between the glucocorticoid receptor and other transcription factors: Molecular aspects
Kassel, O., & Herrlich, P. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.07.003 · Cited by 277 · see citing works
Meduri, G. U., Tolley, E. A., Chrousos, G. P., & Stentz, F. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.7.2106014 · Cited by 265 · see citing works
De Bosscher, K. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00297-6 · Cited by 264 · see citing works
Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids
Almawi, W., & Melemedjian, O. (2002) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0280069 · Cited by 242 · see citing works
Huai, W., Zhao, R., Song, H., Zhao, J., Zhang, L., Zhang, L., Gao, C., Han, L., & Zhao, W. (2014) · Nature Communications · doi:10.1038/ncomms5738 · Cited by 211 · see citing works
Ras/Mitogen-Activated Protein Kinase Signaling Activates Ets-1 and Ets-2 by CBP/p300 Recruitment
Foulds, C. E., Nelson, M. L., Blaszczak, A. G., & Graves, B. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10954-10964.2004 · Cited by 190 · see citing works
Carlson, D. B., & Perdew, G. H. (2002) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.10051 · Cited by 184 · see citing works
Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome
Vockley, C. M., D’Ippolito, A. M., McDowell, I. C., Majoros, W. H., Safi, A., Song, L., Crawford, G. E., & Reddy, T. E. (2016) · Cell · doi:10.1016/j.cell.2016.07.049 · Cited by 182 · see citing works
Meduri, G. U., Muthiah, M. P., Carratù, P., Eltorky, M., & Chrousos, G. P. (2005) · Neuroimmunomodulation · doi:10.1159/000091126 · Cited by 167 · see citing works
Novel glucocorticoid receptor coactivator effector mechanisms
Jenkins, B. D., Pullen, C. B., & Darimont, B. D. (2001) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(00)00357-x · Cited by 150 · see citing works
Doucas, V., Shi, Y., Miyamoto, S., West, A., Verma, I., & Evans, R. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220413297 · Cited by 125 · see citing works
Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms
Ohmori, Y., & Hamilton, T. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006227200 · Cited by 106 · see citing works
Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells
Scheller, K., Seibel, P., & Sekerist, C. E. (2003) · International review of cytology · doi:10.1016/s0074-7696(02)22011-2 · Cited by 73 · see citing works
Bladh, L.-G., Lidén, J., Dahlman-Wright, K., Reimers, M., Nilsson, S., & Okret, S. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.005801 · Cited by 49 · see citing works
- Authors
- Sheppard, K.-A., Phelps, K. M., Williams, A. J., Thanos, D., Glass, C. K., Rosenfeld, M. G., Gerritsen, M. E., & Collins, T.
- Affiliations
- Brigham and Women's Hospital (US)
- Columbia University (US)
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Genentech (US)
- Corresponding author
- Collins, Tucker
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 273
- Issue
- 45
- Pages
- 29291-29294
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1972692051
- Cited by
- 305
- References
- 3
- Citations by year
- 2025: 4 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 10.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- glucocorticoid receptor, NF-κB, RelA/p65, CREB-binding protein, SRC-1, transcriptional coactivator, transcriptional repression, inflammatory gene expression, glucocorticoid signaling
- MeSH terms
- Animals, Base Sequence, Cattle, Cell Nucleus, Cells, Cultured, Endothelium, Vascular, Nuclear Proteins, Oligodeoxyribonucleotides, Protein Binding, Receptors, Glucocorticoid, Transcription Factors, Signal Transduction, Trans-Activators, Gene Expression, NF-kappa B, COS Cells, Receptor Cross-Talk, CREB-Binding Protein, Histone Acetyltransferases, Nuclear Receptor Coactivator 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
