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A more recent version of this article appeared on April 1, 2006
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Submitted on November 18, 2005
Revised on January 25, 2006
Accepted on February 2, 2006
Graduate Programs in *Genomic Sciences and
Toxicology and the
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606;
Nikon Instruments, Melville, NY 11747
Monitoring Editor: William Tansey
We have reported that extracts prepared from many human and mouse cell lines show little or no Sp2 DNA-binding activity, and that Sp2 has little or no capacity to stimulate transcription of promoters that are activated by Sp1, Sp3, and Sp4. Using an array of chimeric Sp1/Sp2 proteins we showed further that Sp2 DNA-binding activity and trans-activation are each negatively regulated in mammalian cells. As part of an ongoing effort to study Sp2 function and regulation we characterized its subcellular localization in comparison with other Sp-family members in fixed and live cells. We report that (i) Sp2 localizes largely within subnuclear foci associated with the nuclear matrix, and (ii) these foci are distinct from promyelocytic oncogenic domains and appear to be stable during an 18 h time course of observation. Deletion analyses identified a 37 amino acid sequence spanning the first zinc-"finger" that is sufficient to direct nuclear matrix association, and this region also encodes a bipartite nuclear localization sequence. A second nuclear matrix targeting sequence is encoded within the Sp2 trans-activation domain. We conclude that Sp2 preferentially associates with the nuclear matrix and speculate that this subcellular localization plays an important role in the regulation of Sp2 function.
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