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Molecular and Cellular Biology, September 1998, p. 5128-5139, Vol. 18, No. 9
Department of Physiology,
Received 19 December 1997/Returned for modification 19 February
1998/Accepted 2 June 1998
Using the DNA-binding domain of androgen receptor (AR) as a bait in
a yeast two-hybrid screening, we have identified a small nuclear RING
finger protein, termed SNURF, that interacts with AR in a
hormone-dependent fashion in both yeast and mammalian cells. Physical
interaction between AR and SNURF was demonstrated by
coimmunoprecipitation from cell extracts and by protein-protein affinity chromatography. Rat SNURF is a highly hydrophilic protein consisting of 194 amino acid residues and comprising a consensus C3HC4 zinc finger (RING) structure in the
C-terminal region and a bipartite nuclear localization signal near the
N terminus. Immunohistochemical experiments indicated that SNURF is a
nuclear protein. SNURF mRNA is expressed in a variety of human and rat
tissues. Overexpression of SNURF in cultured mammalian cells enhanced
not only androgen, glucocorticoid, and progesterone receptor-dependent
transactivation but also basal transcription from steroid-regulated
promoters. Mutation of two of the potential Zn2+
coordinating cysteines to serines in the RING finger completely abolished the ability of SNURF to enhance basal transcription, whereas
its ability to activate steroid receptor-dependent transcription was
maintained, suggesting that there are separate domains in SNURF that
mediate interactions with different regulatory factors. SNURF is
capable of interacting in vitro with the TATA-binding protein, and the
RING finger domain is needed for this interaction. Collectively, we
have identified and characterized a ubiquitously expressed RING finger
protein, SNURF, that may function as a bridging factor and regulate
steroid receptor-dependent transcription by a mechanism different from
those of previously identified coactivator or integrator proteins.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Identification of a Novel RING Finger Protein as a
Coregulator in Steroid Receptor-Mediated Gene Transcription
*
Corresponding author. Mailing address: Department of
Physiology, Institute of Biomedicine, University of Helsinki, P.O. Box 9 (Siltavuorenpenger 20J), FIN-00014 Helsinki, Finland. Phone: 358-9-1918542. Fax: 358-9-1918681. E-mail:
jorma.palvimo{at}helsinki.fi.
Molecular and Cellular Biology, September 1998, p. 5128-5139, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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