Proteasomes Enhance Androgen Receptor Action

Abstract

Proteasome inhibitors can elicit apoptosis in different cancer cells types. Lin et al. have explored the molecular details of this effect in prostate cancer cell lines where signals mediated by the steroid hormone androgen play a key role in cancer progression. The study reports that proteasome activity is required for androgen receptor (AR) activity. A link between AR activity and the ubiquitin-proteasome pathway had been suspected, as certain AR coregulators contain ubiquitin-protein ligase activity. Treatment of prostate cancer cells with a proteasome inhibitor suppressed AR transactivation and expression of target genes. A block in AR nuclear translocation and AR interaction with certain coregulators suggests that proteasomes may guide AR to its gene targets, as well as mediate interaction with its coregulators. The proteasome inhibitor did not affect the activity of the glucocorticoid receptor nor did it have a general toxic effect on cells. Overexpression of a proteasome core complex increased AR activity. The authors suggest that the ubiquitin-proteasome pathway may play a nonproteolytic role in modulating AR trafficking and recruitment of transcription factors. H. K. Lin, S. Altuwaljri, W. J. Lin, P.-Y. Kan, L. L. Collins, C. Chang, Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with coregulators in prostate cancer cells. J. Biol. Chem. 277 , 36570-36476 (2002). [Abstract] [Full Text]