Steroid hormone receptors exert much of their effects on cellular physiology through regulating the rate of transcription from unique target genes. Much has been learned about the actions of steroid hormone receptors at regulated promoters through model in vitro studies, but it has always been a challenge to extrapolate these mechanistic insights to molecular events that occur in live cells. However, novel insights have recently been gained regarding the nature of receptor encounters with the transcriptional machinery from elegant experimental approaches that used advances gained in biochemical, molecular biological, cell biological, and biophysical disciplines. Although these is no doubt that steroid hormone receptors represent some of the most mobile proteins within the nucleus, they still maintain their ability to orchestrate a highly ordered recruitment of cofactors and coregulators at specific sites and remain accessible to alternative processing pathways that limit their action. As highlighted in this review, there may be interrelationships between seemingly distinct pathways of receptor trafficking and processing within the nucleus that impact receptor action at regulated promoters.
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