• M Hiramoto, N Shimizu, K Sugimoto, J Tang, Y Kawakami, M Ito, S Aizawa, H Tanaka, I Makino, and H Handa.
• Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
• J. Immunol. 1998 Jan 15; 160 (2): 810-9.

AbstractThe activation of NF-kappa B consists of at least three steps: degradation of I kappa B alpha, translocation of NF-kappa B into the nucleus, ai post-translational modification of NF-kappa B (e.g., phosphorylation of p65). In the present study, we found that a novel quinone derivative E3330 selectively inhibited NF-kappa B-mediated gene expression without affecting any of these steps. E3330, when included in the culture medium, suppressed NF-kappa B DNA-binding activity in PMA-induced Jurkat cell nuclear extracts, suggesting that the inhibition by E3330 of NF-kappa B-mediated gene expression was due to its ability to suppress NF-kappa B DNA-binding activity. Fractionation of the nuclear extracts by column chromatography revealed that a nuclear factor enhanced NF-kappa B DNA-binding activity and that this enhancing activity was interrupted after treatment with E3330. Moreover, a major polypeptide with a molecular mass of 40 kDa was found to be in the highly purified fraction containing the NF-kappa B-enhancing activity and predominantly bind E3330. Taken together, these results suggest that the NF-kappa B activity, after dissociation from I kappa B, is enhanced by a nuclear factor that is active irrespective of PMA treatment, and the nuclear factor-mediated enhancement is selectively inhibited by E3330. Thus, we conclude that E3330 may belong to a novel class of anti-NF-kappa B drugs.

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