ESTROGEN-RECEPTOR ACTIVATION FUNCTION 1 WORKS BY BINDING P160 COACTIVATOR PROTEINS

Estrogen receptor-alpha contains two transactivation functions, a weak constitutive activation function (AF-1) and a hormone-dependent activ ation function (AF-2). AF-2 works by recruiting a large coactivator co mplex, 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 cen ter of the p160 molecule, AF-1 binds to sequences near the p160 C term inus. We propose that the ability of AF-1 and AF-2 to interact with se parate surfaces of the same coactivator is important for the ability o f these transactivation functions to synergize.