TRANSCRIPTION Calcium/Calmodulin and the Estrogen Receptor

A link between estrogen receptor (ER) 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 ER transcriptional activity requires calcium-calmodulin. They identified a region in the ER that was necessary and sufficient for ER to bind to calmodulin-Sepharose, and this interaction required the presence of calcium. Expression of either deletion mutants covering the calmodulin-binding region or ER 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 ER 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 ER activity. Similar results on estrogen-stimulated transcriptional activity were reported for the endogenous gene pS2 in COS-7 cells or MCF-7 transfected with ER mutants or calmodulin mutant or exposed to chelating agents. Analysis of the structure of the ER, 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- is dependent on Ca²⁺/calmodulin. J. Biol. Chem. 280, 13097-13104 (2005). [Abstract] [Full Text]