Regulation of NF-kappa B through the nuclear processing of p105 (NF-kappa B1) in Epstein-Barr virus-immortalized B cell lines.
Transcription factors of the NF-kappa B/Rel family are retained in the cytoplasm as inactive complexes through association with I kappa B inhibitory proteins. Several NF-kappa B activators induce the proteolysis of I kappa B proteins, which results in the nuclear translocation and DNA binding of NF-kappa B complexes. Here, we report a novel mechanism of NF-kappa B regulation mediated by p105 (NF-kappa B1) precursor of p50 directly at the nuclear level. In Epstein-Barr virus-immortalized B cells, p105 was found in the nucleus, where it was complexed with p65. In concomitance with NF-kappa B activation, mitomycin C induced the processing of p105 to p50 in the nucleus, while it did not affect the steady-state protein levels of I kappa B alpha and p105 in the cytoplasm. Differently, phorbol 12-myristate 13-acetate induced a significant proteolysis of both I kappa B alpha and p105 in the cytoplasm, while it did not affect the protein level of p105 in the nucleus. These results suggest that in Epstein-Barr virus-positive B cell lines the nuclear processing of p105 can contribute to NF-kappa B activation in response to specific signaling molecules, such as DNA-damaging agents.
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi Federico II, Naples, Italy.
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D001402:B-Lymphocytes / Q000166:cytology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002472:Cell Transformation, Viral; D004247:DNA; D004854:Herpesvirus 4, Human / Q000502:physiology*; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001426:Bacterial Proteins; C086269:Epstein-Barr virus-associated protein p105, bacteria; D016328:NF-kappa B; D016685:Mitomycin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate