Androgen receptor interacts with a novel MYST protein, HBO1

The androgen receptor (AR), a member of the nuclear receptor superfamily, p lays a central role in male sexual differentiation and prostate cell prolif eration. Results of-treating prostate cancer by androgen ablation indicate that signals mediated through AR are critical for the growth of these tumor s. Like other nuclear receptors, AR exerts its transcriptional function by binding to cis-elements upstream of promoters and interacting with. other t ranscriptional factors (e.g. activators, repressors and modulators). To det ermine the mechanism of AR-regulated transcription, we used the yeast two-h ybrid system to identify AR-associated proteins. One of the proteins we ide ntified is identical to the human origin recognition complex-interacting pr otein termed HBO1. A ligand-enhanced interaction between AR and HBO1 was fu rther confirmed in vivo and in vitro. Immunofluorescence experiments showed that HBO1 is a nuclear:protein,:and Northern blot analysis revealed that i t is ubiquitously expressed, with the highest levels present inhuman testis . HBO1 belongs to the MYST family, which is characterized by a highly conse rved C2HC zinc finger and a putative histone acetyltransferase domain. Surp risingly, two yeast members of the MYST family, SAS2: and SAS3, have been s hown to function as transcription silencers, despite the presence of the hi stone acetyltransferase domain. Using a GAL4 DNA-binding domain assay, we m apped a transcriptional repression domain within the N-terminal region of H BO1. Transient transfection experiments revealed that HBO1 specifically rep ressed AR-mediated transcription in both CV-1 and PC-3 cells. These results indicate that HBO1 is a new AR-interacting protein capable of modulating A R activity. It could play a significant role in regulating AR-dependent gen es in normal and prostate cancer cells.