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Expression of the GTP-binding protein (Gαs) is repressed by the nuclear factor κB RelA subunit in human myometrium

Lookup NU author(s): Emeritus Professor Nick Europe-Finner, Professor Steve RobsonORCiD


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In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. The onset of parturition is itself associated with increases in a number of proinflammatory mediators, many of which are regulated by the nuclear factor κB (NF-κB) family of transcription factors. Recently, we have provided evidence that the RelA NF-κB subunit associates with protein kinase A in pregnant myometrial tissue, suggesting links with the Gαs/cAMP/protein kinase A pathway. TNFα is a potent activator of NF-κB, and levels of this cytokine are increased within the myometrium at term. In the current study, using primary cultures of myometrial cells, TNFα was observed to repress expression of Gκs while, at the same time, stimulating NF-κB activity. Furthermore, this effect could be replicated by exposure to bacterial lipopolysaccharide and exogenous expression of RelA. Moreover, TNFα was seen to repress endogenous Gαs mRNA expression as judged by RT-PCR analyses. Using the chromatin immunoprecipitation assay, we show that RelA did not bind directly to the Gαs promoter. Significantly, expression of a coactivator protein, cAMP response element binding protein binding protein, relieved RelA-induced down-regulation of Gαs expression. Together, these data suggest that, in human myometrium, repression of the Gαs gene by NF-κB occurs through a non-DNA binding mechanism involving competition for limiting amounts of cellular coactivator proteins including cAMP response element binding protein binding protein. Copyright © 2005 by The Endocrine Society.

Publication metadata

Author(s): Chapman NR, Smyrnias I, Anumba DOC, Europe-Finner GN, Robson SC

Publication type: Article

Publication status: Published

Journal: Endocrinology

Year: 2005

Volume: 146

Issue: 11

Pages: 4994-5002

Print publication date: 01/11/2005

ISSN (print): 0013-7227

ISSN (electronic): 1945-7170

Publisher: The Endocrine Society


DOI: 10.1210/en.2005-0533

PubMed id: 16081638


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