Nuclear Targeted Suppression of NF-κB Activity by the Novel Quinone Derivative E3330
1998; American Association of Immunologists; Volume: 160; Issue: 2 Linguagem: Inglês
10.4049/jimmunol.160.2.810
ISSN1550-6606
AutoresMasaki Hiramoto, Noriaki Shimizu, Kotaro Sugimoto, Jianwei Tang, Yutaka Kawakami, Masaharu Ito, Shin Aizawa, Hirotoshi Tanaka, Isao Makino, Hiroshi Handa,
Tópico(s)Bioactive Compounds and Antitumor Agents
ResumoAbstract The activation of NF-κB consists of at least three steps: degradation of IκBα, translocation of NF-κB into the nucleus, and post-translational modification of NF-κB (e.g., phosphorylation of p65). In the present study, we found that a novel quinone derivative E3330 selectively inhibited NF-κB-mediated gene expression without affecting any of these steps. E3330, when included in the culture medium, suppressed NF-κB DNA-binding activity in PMA-induced Jurkat cell nuclear extracts, suggesting that the inhibition by E3330 of NF-κB-mediated gene expression was due to its ability to suppress NF-κB DNA-binding activity. Fractionation of the nuclear extracts by column chromatography revealed that a nuclear factor enhanced NF-κB 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-κB-enhancing activity and predominantly bind E3330. Taken together, these results suggest that the NF-κB activity, after dissociation from IκB, 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-κB drugs.
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