Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells

Androgen signaling influences the development and growth of prostate carcin oma. The transcriptional activity of androgen receptor (AR) is regulated by positive or negative transcriptional cofactors, We report here that PIAS1, PIAS3, and PIASy of the protein inhibitor of activated STAT (PIAS) family, which are expressed in human prostate, display distinct effects on AR-medi ated gene activation in prostate cancer cells. While PIAS1 and PIAS3 enhanc e the transcriptional activity of AR, PIASy acts as a potent inhibitor of A R in prostate cancer cells, The effects of PIAS proteins on AR are competit ive. PIASy binds to AR but does not affect the DNA binding activity of AR. An NH2-terminal LXXLL signature motif of PIASy, although not required for P IASy-AR interaction, is essential for the transrepression activity of PIASy , Our results identify PIASy as a transcriptional corepressor of AR and sug gest that different PIAS proteins have distinct effects on AR signaling in prostate cancer cells.