Coregulator Small Nuclear RING Finger Protein (SNURF) Enhances Sp1- and Steroid Receptor-mediated Transcription by Different Mechanisms

• Published in: The Journal of biological chemistry Vol. 275; no. 1; pp. 571 - 579
• Main Authors: Poukka, H, Aarnisalo, P, Santti, H, Jänne, O A, Palvimo, J J
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 07-01-2000
• Subjects: Amino Acid Sequence; Androgen-Insensitivity Syndrome - genetics; Breast Neoplasms, Male - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Humans; Male; Molecular Sequence Data; Nuclear Localization Signals; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Point Mutation; Promoter Regions, Genetic; Protein Binding; Receptors, Androgen - metabolism; Recombinant Proteins - metabolism; SNURF protein; Sp1 protein; Sp1 Transcription Factor - metabolism; steroid hormone receptors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Zinc Fingers - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.1.571

The small nuclear RING finger protein SNURF is not only a coactivator in steroid receptor-dependent transcription but also
activates transcription from steroid-independent promoters. In this work, we show that SNURF, via the RING finger domain,
enhances protein binding to Sp1 elements/GC boxes and interacts and cooperates with Sp1 in transcriptional activation. The
activation 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 AR are sufficient for
contacting SNURF. The nuclear localization signal in the boundary between ZFR and the hinge region participates in the association
of AR with SNURF, and a receptor mutant lacking the C-terminal part of the bipartite nuclear localization signal shows attenuated
response to coexpressed SNURF. Some AR ZFR point mutations observed in patients with partial androgen insensitivity syndrome
or male breast cancer impair the interaction of AR with SNURF and also render AR refractory to the transcription-activating
effect of SNURF. Collectively, SNURF modulates the transcriptional activities of androgen receptor and Sp1 via different domains,
and it may act as a functional link between steroid- and Sp1-regulated transcription.