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Sci. STKE, 26 September 2000
Vol. 2000, Issue 51, p. tw1
[DOI: 10.1126/stke.2000.51.tw1]


Nuclear receptors Anti-inflammatory contacts

The NF-{kappa}B transcription factor is a key mediator of gene transcription in response to proinflammatory stimuli. Glucocorticoids, which act through nuclear receptors that are themselves transcription factors, are widely used clinically to suppress inflammation, but it has been unclear precisely how glucocorticoids inhibit NF-{kappa}B-induced expression of target genes. Some results imply that glucocorticoids increase the expression of the NF-{kappa}B inhibitor I{kappa}B, whereas other studies have shown an interaction of the glucocorticoid receptor (GR) with NF-{kappa}B. Nissen and Yamamoto now show that the GR interacts with NF-{kappa}B at target promoters. Their experiments indicate that the DNA binding domain of the GR interacts, not with DNA in this instance, but with the dimerization domain of the RelA subunit of NF-{kappa}B. This interaction did not disrupt interaction of NF-{kappa}B with DNA. Rather, the inhibitory effect appeared to result from inhibition of phosphorylation of the COOH-terminal domain of RNA polymerase II in preinitiation complexes. The authors propose that the GR might recruit a corepressor such as a phosphatase. Clearly, the "DNA binding" domain of the GR is not simple. It must contain at least two functional surfaces that operate in distinct contexts.

Nissen, R.M., and Yamamoto, K.R. (2000) The glucocorticoid receptor inhibits NF{kappa}B by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev. 14: 2314-2329. [Abstract] [Full Text]

Citation: Anti-inflammatory contacts. Sci. STKE 2000, tw1 (2000).

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