The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor

Abstract

Members of the Bag-1 family of cochaperones regulate diverse cellular processes including the action of steroid hormone receptors. The largest member of this family, Bag-1L, enhances the transactivation function of the androgen receptor. This occurs primarily through interaction with the NH₂ and COOH termini of the receptor. At the NH₂ terminus of the receptor, Bag-1L interacts with a region termed τ5. Bag-1M, a naturally occurring variant of Bag-1L that binds to τ5 but is defective in the COOH-terminal interaction, is less efficient in enhancing the transactivation function of the receptor. Surface plasmon resonance and transfection studies showed that the molecular chaperone Hsp70 contributes to the binding of Bag-1L to τ5 and to the regulation of the transactivation function of the androgen receptor. Chromatin immunoprecipitation studies demonstrated that the androgen receptor, Hsp70, and Bag-1L are all targeted to the androgen response elements of the gene that encodes prostate-specific antigen. These studies demonstrate the regulation of transcriptional activity of androgen receptor by a molecular chaperone-cochaperone complex.