Subcellular localization and mechanisms of nucleocytoplasmic distribution of p202, an interferon-inducible candidate for lupus susceptibility.
Increased expression of p202 (52 kDa), an interferon (IFN)-inducible murine protein, in splenic cells (B- and T-cells) derived from female mice of the lupus-prone strains is correlated with increased susceptibility to develop systemic lupus erythematosus. However, the molecular mechanisms remain unclear. Our previous studies have indicated that, in IFN-treated fibroblasts, p202 is detected both in the cytoplasm and in the nucleus. Moreover, in the cytoplasm, a fraction of p202 associates with a membranous organelle. Here we report that, in the cytoplasm, a fraction of p202 associated with mitochondria. Additionally, we found that the constitutive p202 is primarily detected in the cytoplasm. Remarkably, the IFN treatment of cells potentiated nuclear accumulation of p202. Our observations are consistent with the possibility that IFN signaling regulates p202 levels as well as its nucleocytoplasmic distribution. These observations will serve as a basis to elucidate the molecular mechanisms by which p202 contributes to lupus susceptibility.
Department of Radiation Oncology, Stritch School of Medicine, Loyola University Medical Center, 60153 Maywood, IL, USA. dchoube@lumc.edu
Divaker
D
Choubey
Rocky
R
Pramanik
Hong
H
Xin
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004198:Disease Susceptibility; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D007370:Interferon Type I / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008177:Lupus Vulgaris / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008928:Mitochondria / Q000378:metabolism; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; C092537:Ifi202b protein, mouse; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins