ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein inhibitor of activated STAT) proteins differ in their ability to modulate steroid receptor-dependent transcriptional activation

Steroid receptors mediate their actions by using various coregulatory prote ins. We have recently characterized ARIP3/PIASx alpha as an androgen recept or (AR)-interacting protein (ARIP) that belongs to the PIAS [protein inhibi tor of activated STAT (signal transducer and activator of transcription)] p rotein family implicated in the inhibition of cytokine signaling. We have a nalyzed herein the roles that four different PIAS proteins (ARIP3/PIASx alp ha, Miz1/PIASx beta, GBP/PIAS1, and PIAS3) play in the regulation of steroi d receptor- or STAT-mediated transcriptional activation. AII PIAS proteins are able to coactivate steroid receptor-dependent transcription but to a di fferential degree, depending on the receptor, the promoter, and the cell ty pe. Miz1 and PIAS1 are more potent than ARIP3 in activating AR function on minimal promoters. With the natural probasin promoter, PIAS proteins influe nce AR function more divergently, in that ARIP3 represses, but Miz1 and PIA S1 activate it. Miz1 and PIAS1 possess inherent transcription activating fu nction, whereas ARIP3 and PIAS3 are devoid of this feature. ARIP3 enhances glucocorticoid receptor-dependent transcription more efficiently than Miz1 or PIAS1, and all PIAS proteins also activate estrogen receptor- and proges terone receptor-dependent transcription but to a dissimilar degree. The sam e amounts of PIAS proteins that modulate steroid receptor-dependent transcr iption influence only marginally transactivation mediated by various STAT p roteins. It remains to be established whether the PIAS proteins play a more significant physiological role in steroid receptor than in cytokine signal ing.