Coregulator small nuclear RING finger protein (SNURF) enhances Sp1-and steroid receptor-mediated transcription by different mechanisms

The small nuclear RING finger protein SNURF is not only a coactivator in st eroid receptor-dependent transcription but also activates transcription fro m steroid-independent promoters. In this work, we show that SNURF, via the RING finger domain, enhances protein binding to Sp1 elements/GC boxes and i nteracts and cooperates with Sp1 in transcriptional activation. The activat ion of androgen receptor (AR) function requires regions other than the RING finger of SNURF, and SNURF does not influence binding of AR to cognate DNA elements. The zinc finger region (ZFR) together with the hinge region of A R are sufficient for contacting SNURF. The nuclear localization signal in t he boundary between ZFR and the hinge region participates in the associatio n of AR with SNURF, and a receptor mutant lacking the C-terminal part of th e bipartite nuclear localization signal shows attenuated response to coexpr essed SNURF. Some AR ZFR point mutations observed in patients with partial androgen insensitivity syndrome or male breast cancer impair the interactio n of AR with SNURF and also render AR refractory to the transcription-activ ating effect of SNURF. Collectively, SNURF modulates the transcriptional ac tivities of androgen receptor and Sp1 via different domains, and it may act as a functional link between steroid- and Sp1-regulated transcription.