摘要
Androgen receptor （AR） is able to promote stress-induced cell death independently of its transcription activity in androgen-independent prostate cancer cells. Yet, the underlying mechanism is incompletely understood. Here, we report that stress-induced proteasomal degradation of AR contributes to its pro-death activity. Upon exposure to ul- traviolet fight and staurosporine, AR underwent proteasomal degradation. Blockade of AR degradation significantly suppressed stress-induced apoptosis in androgen-independent prostate cancer cells. Ectopic expression of the AR N-terminal （AR-N） domain, which lacks DNA- and ligand-binding abilities, led to cell death without any additional death stimuli. Truncation analysis revealed that AR-N domain contains several sub-domains that regulate the pro- death activity of AR, specifically the first 105 amino acids, which function as a minimal pro-death domain acting upstream of caspases. The pro-apoptotic activity of AR N-terminal fragments was suppressed by ectopic expression of Bcl-2 or selected caspase inhibitors. Thus, our results reveal a novel mechanism by which AR promotes stressinduced cell death in androgen-independent prostate cancer cells.
