title: Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.
abstract: 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.
authors.affiliation: Hematology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Futaki
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Kajigaya
authors.forename: J M
authors.initials: JM
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D011233:Precipitin Tests; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C499909:FANCG protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D010750:Phosphoproteins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha