We present an integrated model of hERα-mediated transcription where both unliganded and liganded receptors cycle on estrogen-responsive promoters. Using ChIP, FRAP, and biochemical analysis we evaluate hERα at several points in these cycles, establishing the ubiquitination status and subnuclear distribution of hERα, its mobility, the kinetics of transcriptional activation, and the cyclic recruitment of E3 ligases and the 19S regulatory component of the proteasome. These experiments, together with an evaluation of the inhibition of transcription and proteasome action, demonstrate that proteasome-mediated degradation and hERα-mediated transactivation are inherently linked and act to continuously turn over hERα on responsive promoters. Cyclic turnover of hERα permits continuous responses to changes in the concentration of estradiol.