Nuclear Receptor Partner

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Science  13 Dec 2013:
Vol. 342, Issue 6164, pp. 1293
DOI: 10.1126/science.342.6164.1293-b

Drugs that activate glucocorticoid nuclear homone receptors are commonly used in the clinic for their anti-inflammatory actions, or to slow the growth of some cancers. The ways in which these receptors, which function as transcription factors in the nucleus, modulate a broad set of genes that make up a quarter of the genome are not fully understood. Revollo et al. show that another transcription factor, HES1 (hairy and enhancer of split-1), has a general role to restrain glucocorticoid-dependent gene expression. HES1 is well known for its function during development in another signaling pathway, the Notch signaling pathway. Revolo et al. show that in adult mice, HES1 acts at glucocorticoid-responsive genes to inhibit transcription and that it also strongly influences the range of genes that are responsive to glucocorticoids. In order to regulate many of its targets, it appears that a primary effect of the glucocorticoid receptor is to first repress transcription of the gene encoding HES1. This relieves inhibition by HES1 and allows the glucocoricoid receptor to activate its targets and produce its wide-ranging effects that support physiological responses to stress.

Sci. Signal. 6, 10.1126/scisignal.2004389 (2013).

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