Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.
Fanconi anemia (FA) is a genetic syndrome characterized by bone marrow failure, birth defects, and a predisposition to malignancy. At this time, six FA genes have been identified, and several gene products have been found to interact in a protein complex. FA cells appear to overexpress the proinflammatory cytokine, tumor ... necrosis factor-alpha (TNF-alpha). We therefore examined the effects of TNF-alpha on the regulation of FA complementation group proteins, FANCG and FANCA. We found that treatment with TNF-alpha induced FANCG protein expression. FANCA was induced concurrently with FANCG, and the FANCA/FANCG complex was increased in the nucleus following TNF-alpha treatment. Inactivation of inhibitory kappa B kinase-2 modulated the expression of FANCG. We also found that both nuclear and cytoplasmic FANCG fractions were phosphorylated. These results show that FANCG is a phosphoprotein and suggest that the cellular accumulation of FA proteins is subject to regulation by TNF-alpha signaling.
Mesh Terms:
Blotting, Western, Cell Line, Cell Nucleus, Cytoplasm, DNA, Recombinant, DNA-Binding Proteins, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group G Protein, Hela Cells, Humans, Phosphoproteins, Phosphorylation, Plasmids, Precipitin Tests, Proteins, Transfection, Tumor Necrosis Factor-alpha, Up-Regulation
Blotting, Western, Cell Line, Cell Nucleus, Cytoplasm, DNA, Recombinant, DNA-Binding Proteins, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group G Protein, Hela Cells, Humans, Phosphoproteins, Phosphorylation, Plasmids, Precipitin Tests, Proteins, Transfection, Tumor Necrosis Factor-alpha, Up-Regulation
Biochem. Biophys. Res. Commun.
Date: Feb. 23, 2001
PubMed ID: 11181053
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