LNCaP prostate cancer cell lines overexpressing wild-type or GARRPR-mutant Bag-1L

The BF-3 pocket of the androgen receptor (AR) has been identified as an allosteric modulator of the transactivation function of the AR. We now demonstrate that a duplicated GARRPR motif at the N-terminus of the cochaperone Bag-1L functions through this BF-3 domain. Amino acid exchanges in these two motifs impair binding of Bag-1L to the AR but increase the androgen-dependent activation of a subset of AR-target genes. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the receptor.

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Jehle K, Cato L, Neeb A, Muhle-Goll C, Jung N, Smith EW, Buzon V, Carbó LR, Estébanez-Perpiñá E, Schmitz K, Fruk L, Luy B, Chen Y, Cox MB, Bräse S, Brown M, Cato AC