Subcellular recruitment of fibrillarin to nucleoplasmic proteasomes: Implications for processing of a nucleolar autoantigen

被引:49
作者
Chen, M
Rockel, T
Steinweger, G
Hemmerich, P
Risch, J
von Mikecz, A [1 ]
机构
[1] Univ Dusseldorf, Jr Res Grp Mol Cell Biol, Inst Environm Hlth Res, D-4000 Dusseldorf, Germany
[2] Inst Mol Biotechnol, Dept Mol Biol, Jena, Germany
[3] Rhein Westfal TH Aachen, Ctr Comp, Aachen, Germany
关键词
D O I
10.1091/mbc.02-05-0083
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 focusing 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. Because proteasomes are absent from the nucleolus, a recruitment system was used to analyze 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.
引用
收藏
页码:3576 / 3587
页数:12
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