Estrogen Receptor Activation Function 1 Works by Binding p160 Coactivator Proteins

• DOI: 10.1210/mend.12.10.0185
• Publication Date: 2014-01-08T12:29:52Z
• Authors: Paul Webb; Phuong Nguyen; Jeanette Shinsako; Carol Anderson; Weijun Feng; Mimi P. Nguyen; Dagang Chen; Shih-Ming Huang; Sujatha Subramanian; Eileen McKinerney; Benita S. Katzene...; Michael R. Stallcup; Peter J. Kushner
• Keywords: 0301 basic medicine; Binding Sites; Estrogen Receptor alpha; Nuclear Proteins; Cell Cycle Proteins; CREB-Binding Protein; Peptide Fragments; Recombinant Proteins; Nuclear Receptor Coactivator 3; Nuclear Receptor Coactivator 2; Tamoxifen; 03 medical and health sciences; Nuclear Receptor Coactivator 1; Receptors, Estrogen; Acetyltransferases; Trans-Activators; Estrogen Receptor beta; Humans; p300-CBP Transcription Factors; HeLa Cells; Histone Acetyltransferases; Transcription Factors

Estrogen receptor-alpha contains two transactivation functions, a weak constitutive activation function (AF-1) and a hormone-dependent activation function (AF-2). AF-2 works by recruiting a large coactivator complex, composed of one or more p160s, CREB-binding protein (CBP)/p300, and P/CAF (p300 and CBP-associated factor), via direct contacts with the p160s. We report here that independent AF-1 activity also requires p160 contacts. Unlike AF-2, which binds signature NR boxes in the center of the p160 molecule, AF-1 binds to sequences near the p160 C terminus. We propose that the ability of AF-1 and AF-2 to interact with separate surfaces of the same coactivator is important for the ability of these transactivation functions to synergize.