Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter

Calmodulin (CaM) has been reported to have affinity for the estrogen recept or (ER:), Observations reported here reveal a direct physical interaction b etween purified CaM and ER, This direct ER-CaM interaction may he an initia l event preceding the assembly of ER plus auxiliary proteins into the activ e ER complex with its DNA motif the estrogen response element. We demonstra te that CaM is an integral component of this complex by using a system reco nstituted from purified ER and nuclear extract from ER-negative breast canc er cells and also with ER-depleted nuclear extract of an ER-positive breast cancer cell line. Although CaM is essential for formation of this complex, it is not sufficient, suggesting roles also of auxiliary proteins. CaM als o is functionally required for activation of an ER-responsive promoter, in the 17 beta-estradiol-ER pathway of hormone action and regulation of 17 bet a-estradiol-responsive gene expression that is associated with proliferatio n of mammary epithelial cells.