The Estrogen Receptor Enhances AP-1 Activity by Two Distinct Mechanisms with Different Requirements for Receptor Transactivation Functions

• DOI: 10.1210/mend.13.10.0357
• Publication Date: 2014-01-08T17:29:48Z
• Authors: Paul Webb; Phuong Nguyen; Cathleen Valentine; Gabriela N. Lopez; Grace R. Kwok; Eileen McInerney; Benita S. Katzene...; Eva Enmark; Jan-Åke Gustafsson; Stefan Nilsson; Peter J. Kushner
• Keywords: Estrogen receptor alpha; Hormone response element; Antiestrogen; Estrogen receptor beta

Estrogen receptors (ERs α and β) enhance transcription in response to estrogens by binding estrogen elements (EREs) within target genes utilizing transactivation functions (AF-1 AF-2) recruit p160 coactivator proteins. The ERs also antiestrogens modulating the activity of AP-1 protein complex. Here, we examine role AF-1 AF-2 ER action at sites. responses sites require integrity ERα activation surfaces complementary on GRIP1 (glucocorticoid receptor interacting 1), NID/AF-1 region, NR boxes. Thus, estrogen-liganded utilizes same protein-protein contacts transactivate EREs In contrast, antiestrogen are strongly inhibited weakly AF-2. Indeed, truncations that lack presence antiestrogens, but not estrogens. This phenotype resembles ERβ, which naturally lacks constitutive activity. We conclude responsive distinct mechanisms with different requirements for functions. suggest enhances via interactions p160s speculate antiestrogen-liganded corepressors.