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A more recent version of this article appeared on October 1, 2002
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Submitted on December 4, 2001
Revised on May 29, 2002
Accepted on July 16, 2002
1 Junior Research Group of Molecular Cell Biology, Institute of Environmental Health Research, Heinrich-Heine-University, Düsseldorf, Germany
2 Department of Molecular Biology, Institute of Molecular Biotechnology, Jena, Germany
3 Computing Center, Technical University, Aachen, Germany
* Corresponding author. E-mail address: mikecz{at}uni-duesseldorf.de.
A prerequisite for proteins to interact in a cell is that they are present in the same intracellular compartment. Although it is generally accepted that proteasomes occur in both, the cytoplasm and the nucleus, research has been focussing on cytoplasmic protein breakdown and antigen processing, respectively. Thus, little is known on the functional organization of the proteasome in the nucleus. Here we report that within the nucleus 20S and 26S proteasomes occur throughout the nucleoplasm, and partially colocalize with splicing factor-containing speckles. Since proteasomes are absent from the nucleolus, a recruitment system was used to analyse the molecular fate of nucleolar protein fibrillarin: Subtoxic concentrations of mercuric chloride (HgCl2) induce subcellular redistribution of fibrillarin and substantial colocalization (33%) with nucleoplasmic proteasomes in different cell lines, and in primary cells isolated from mercury-treated mice. Accumulation of fibrillarin and fibrillarin-ubiquitin conjugates in lactacystin-treated cells suggests that proteasome-dependent processing of this autoantigen occurs upon mercury induction. The latter observation might constitute the cell biological basis of autoimmune responses that specifically target fibrillarin in mercury-mouse models and scleroderma.
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