Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells.
Androgen signaling influences the development and growth of prostate carcinoma. 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-mediated gene activation in prostate cancer cells. While PIAS1 and PIAS3 enhance the transcriptional activity of AR, PIASy acts as a potent inhibitor of AR in prostate cancer cells. The effects of PIAS proteins on AR are competitive. 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 PIASy-AR interaction, is essential for the transrepression activity of PIASy. Our results identify PIASy as a transcriptional corepressor of AR and suggest that different PIAS proteins have distinct effects on AR signaling in prostate cancer cells.
Gross
M
M
Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, California, CA 90095, USA.
Liu
B
B
Tan
J
J
French
F S
FS
Carey
M
M
Shuai
K
K
D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D000075223:Poly-ADP-Ribose Binding Proteins; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000728:Androgens; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D011944:Receptors, Androgen; D004247:DNA; D017430:Prostate-Specific Antigen