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CBP is a dosage-dependent regulator of nuclear factor-kappa B suppression by the estrogen receptor

Academic Article
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Overview

authors

  • Nettles, Kendall
  • Gil, G.
  • Nowak, J.
  • Metivier, R.
  • Sharma, V. B.
  • Greene, G. L.

publication date

  • 2008

journal

  • Molecular Endocrinology  Journal

abstract

  • The estrogen receptor (ER) protects against debilitating effects of the inflammatory response by inhibiting the proinflammatory transcription factor nuclear factor-kappaB (NFkappaB). Heretofore cAMP response element-binding protein (CREB)-binding protein (CBP) has been suggested to mediate inhibitory cross talk by functioning either as a scaffold that links ER and NFkappaB or as a required cofactor that competitively binds to one or the other transcriptional factor. However, here we demonstrate that ER is recruited to the NFkappaB response element of the MCP-1 (monocyte chemoattractant protein-1) and IL-8 promoters and displaces CBP, but not p65, in the MCF-7 breast cancer cell line. In contrast, ER displaced p65 and associated coregulators from the IL-6 promoter, demonstrating a gene-specific role for CBP in integrating inflammatory and steroid signaling. Further, RNA interference and overexpression studies demonstrated that CBP dosage regulates estrogen-mediated suppression of MCP-1 and IL-8, but not IL-6, gene expression. This work further demonstrates that CBP dosage is a critical regulator of gene-specific signal integration between the ER- and NFkappaB-signaling pathways.

subject areas

  • Blotting, Northern
  • CREB-Binding Protein
  • Cell Line, Tumor
  • Chemokine CCL2
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Estradiol
  • Estrogen Receptor alpha
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Humans
  • Immunoprecipitation
  • Interleukin-6
  • Interleukin-8
  • Models, Biological
  • NF-kappa B
  • Polymerase Chain Reaction
  • Protein Binding
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
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Identity

PubMed Central ID

  • PMC2234588

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/me.2007-0324

PubMed ID

  • 17932106
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Additional Document Info

start page

  • 263

end page

  • 272

volume

  • 22

issue

  • 2

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