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Calcium/Calmodulin and the Estrogen Receptor

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Science's STKE  05 Apr 2005:
Vol. 2005, Issue 278, pp. tw128
DOI: 10.1126/stke.2782005tw128

A link between estrogen receptor α (ERα) and calcium and calmodulin has previously been reported, yet this interaction is not widely accepted. Li et al. provide multiple lines of evidence to show that estrogen stimulation of ERα transcriptional activity requires calcium-calmodulin. They identified a region in the ERα that was necessary and sufficient for ERα to bind to calmodulin-Sepharose, and this interaction required the presence of calcium. Expression of either deletion mutants covering the calmodulin-binding region or ERα with point mutations in the calmodulin-binding region in COS-7 cells abolished estrogen-stimulated reporter gene expression. The defective transcriptional activity of the mutant ERα was not due to lack of estrogen binding based on radioligand binding assays. MCF-7 cells treated with a calcium-permeable chelator or transfected with a calmodulin mutant that cannot bind calcium demonstrated impaired estrogen-stimulated reporter gene activity, supporting a role for calcium in ERα activity. Similar results on estrogen-stimulated transcriptional activity were reported for the endogenous gene pS2 in COS-7 cells or MCF-7 transfected with ERα mutants or calmodulin mutant or exposed to chelating agents. Analysis of the structure of the ERα, estrogen, and calmodulin will reveal more about the mechanism of this interaction.

L. Li, Z. Li, D. B. Sacks, The transcriptional activity of estrogen receptor-α is dependent on Ca2+/calmodulin. J. Biol. Chem. 280, 13097-13104 (2005). [Abstract] [Full Text]

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