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Mol Endocrinol. 2008 Feb;22(2):263-72. Epub 2007 Oct 11.

CBP Is a dosage-dependent regulator of nuclear factor-kappaB suppression by the estrogen receptor.

Author information

1
Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA. knettles@scripps.edu

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.

PMID:
17932106
PMCID:
PMC2234588
DOI:
10.1210/me.2007-0324
[Indexed for MEDLINE]
Free PMC Article

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