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J Biol Chem, Vol. 275, Issue 1, 571-579, January 7, 2000
From the 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.
Coregulator Small Nuclear RING Finger Protein (SNURF)
Enhances Sp1- and Steroid Receptor-mediated Transcription by Different
Mechanisms*
,,,§, and¶
Department of Physiology, Institute of
Biomedicine and the § Department of Clinical Chemistry,
University of Helsinki, FIN-00014 Helsinki, Finland
*
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.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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