Fanconi anemia protein complex is a novel target of the IKK signalsome.
Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a ... sixth gene product, FANCD2. Here, we report that FANCA associates with the IkappaB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K > M). When exposed to mitomycin C, cells expressing IKK2 K > M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress.
Mesh Terms:
Adenoviridae, Animals, Binding Sites, Cell Cycle Proteins, Cell Line, Transformed, Cloning, Molecular, DNA-Binding Proteins, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group Proteins, G2 Phase, Genetic Vectors, Hela Cells, Humans, I-kappa B Kinase, I-kappa B Proteins, Kinetics, Mitomycin, Nuclear Proteins, Phosphorylation, Precipitin Tests, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Proteins, Recombinant Proteins, Signal Transduction, Transfection, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques
Adenoviridae, Animals, Binding Sites, Cell Cycle Proteins, Cell Line, Transformed, Cloning, Molecular, DNA-Binding Proteins, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group Proteins, G2 Phase, Genetic Vectors, Hela Cells, Humans, I-kappa B Kinase, I-kappa B Proteins, Kinetics, Mitomycin, Nuclear Proteins, Phosphorylation, Precipitin Tests, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Proteins, Recombinant Proteins, Signal Transduction, Transfection, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques
J. Cell. Biochem.
Date: Sep. 05, 2002
PubMed ID: 12210728
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