Subcellular recruitment of fibrillarin to nucleoplasmic proteasomes: implications for processing of a nucleolar autoantigen.
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 (HgCl(2)) 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.
Chen
Min
M
Junior Research Group of Molecular Cell Biology, Institute of Environmental Health Research, Heinrich-Heine-University, Düsseldorf, Germany.
Rockel
Thomas
T
Steinweger
Gabriele
G
Hemmerich
Peter
P
Risch
Jakob
J
von Mikecz
Anna
A
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D054637:Dual-Specificity Phosphatases; D005260:Female; D006801:Humans; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D025801:Ubiquitin; C047458:fibrillarin; C036825:phosphoprotein C23; C067713:lactacystin; D008627:Mercuric Chloride; C442320:DUSP5 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000111:Acetylcysteine