Coregulator Small Nuclear RING Finger Protein (SNURF) Enhances Sp1- and Steroid Receptor-mediated Transcription by Different Mechanisms*
- From the ‡Department of Physiology, Institute of Biomedicine and the §Department of Clinical Chemistry, University of Helsinki, FIN-00014 Helsinki, Finland
Abstract
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.
Footnotes
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↵* This work was supported by grants from the Medical Research Council (Academy of Finland), the Finnish Foundation for Cancer Research, the Sigrid Jusélius Foundation, the Finnish Medical Society Duodecim, the Finnish Cultural Foundation, Biocentrum Helsinki, and the Helsinki University Central Hospital.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed: Dept. of Physiology, Institute of Biomedicine, University of Helsinki, P. O. Box 9, Siltavuorenpenger 20 J, FIN-00014 Helsinki, Finland. Tel.: 358-9-1918542; Fax: 358-9-1918681; E-mail: jorma.palvimo@helsinki.fi.
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↵2 H. Poukka, P. Aarnisalo, J. J. Palvimo, and O. A. Jänne, unpublished observations.
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↵3 H. Poukka, P. Aarnisalo, O. A. Jänne, and J. J. Palvimo, unpublished observations.
- Abbreviations:
- AR
-
androgen receptor
- ARE
-
androgen response element
- AF
-
activation function
- AD
-
activation domain
- EMSA
-
electrophoretic mobility shift assay
- GR
-
glucocorticoid receptor
- GST
-
glutathione S-transferase
- h
-
human
- r
-
rat
- HRE
-
hormone response element
- LUC
-
luciferase
- NLS
-
nuclear localization signal
- SNURF
-
small nuclear RING finger protein
- Sp1
-
promoter specificity protein 1
- ZF
-
zinc finger
- ZFR
-
ZF region
- tk
-
thymidine kinase
-
- Received July 21, 1999.
- Revision received September 29, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
