AR interaction with DNA motifs in promoter of target genes

When the androgen bound AR translocates from the cytosol to the nucleus, the interaction with the androgen response elements (AREs) on the promoter of androgen target genes will lead to activation of transcription. Structural studies showed that not only the steroid hormone is able to alter nuclear receptor conformation, but also the contact of the receptor with distinct responsive elements on the DNA of gene promoter may alter its form as it was shown for ERs and retinoid X receptor (RXR) (Loven etal. 2001; Yi etal. 2002; Zhao etal. 2000). The interaction between NR and the DNA influences the ability of comodulator recruitment and finally NR signalling. It can be speculated that the conformation mediated by ligands and DNA-binding synergistically influence the interaction with particular comod-ulators which determine the effect on gene transactivation. The overall receptor conformation influenced by ligand and ARE may produce a unique scaffold surface allowing interaction with distinct proteins modulating gene transcription. Further evidence for this so far highly speculative theory is the observation of promoter selective agonistic action of tamoxifen on ER (Berry etal. 1990; Shull etal. 1992; Tzukerman etal. 1994).

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