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Mol. Cells 2002; 14(2): 163-167

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Molecular Design and Biological Activities of NF-kB Inhibitors

Kazuo Umezawa, Chanya Chaicharoenpong

Abstract

NF-kB is a transcription factor that induces inflamma-tory cytokines and anti-apoptotic proteins. We de-signed a new NF-kB inhibitor that is based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethyl-epoxyquino-micin (DHMEQ), inhibited the TNF-a-induced activa-tion of NF-kB, and showed an anti-arthritic effect in mice. Recently, we looked into its mechanism of inhibi-tion. DHMEQ inhibited the TNF-a-induced cellular DNA binding of nuclear NF-kB, but not the phos-phorylation or degradation of I-kB. Moreover, DHMEQ inhibited the TNF-a-induced nuclear accu-mulation of p65, a component of NF-kB. On the other hand, DHMEQ did not inhibit the nuclear transport of Smad2 and the large T antigen. Also, it did not inhibit the TNF-a-induced activation of JNK, but synergisti-cally induced apoptosis with TNF-a in human T cell leukemia Jurkat cells. Therefore, DHMEQ specifically inhibited the NF-kB-activating pathway in the TNF-a-treated cells. Taken together, our data show that DHMEQ is a unique inhibitor of NF-kB that acts at the level of the nuclear translocation. It may be useful as an anti-inflammatory and anticancer agent.

Keywords Apoptosis, DHMEQ, COS-1 Cells, NF-kB, Jurkat Cells

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Mol. Cells 2002; 14(2): 163-167

Published online October 31, 2002

Copyright © The Korean Society for Molecular and Cellular Biology.

Molecular Design and Biological Activities of NF-kB Inhibitors

Kazuo Umezawa, Chanya Chaicharoenpong

Abstract

NF-kB is a transcription factor that induces inflamma-tory cytokines and anti-apoptotic proteins. We de-signed a new NF-kB inhibitor that is based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethyl-epoxyquino-micin (DHMEQ), inhibited the TNF-a-induced activa-tion of NF-kB, and showed an anti-arthritic effect in mice. Recently, we looked into its mechanism of inhibi-tion. DHMEQ inhibited the TNF-a-induced cellular DNA binding of nuclear NF-kB, but not the phos-phorylation or degradation of I-kB. Moreover, DHMEQ inhibited the TNF-a-induced nuclear accu-mulation of p65, a component of NF-kB. On the other hand, DHMEQ did not inhibit the nuclear transport of Smad2 and the large T antigen. Also, it did not inhibit the TNF-a-induced activation of JNK, but synergisti-cally induced apoptosis with TNF-a in human T cell leukemia Jurkat cells. Therefore, DHMEQ specifically inhibited the NF-kB-activating pathway in the TNF-a-treated cells. Taken together, our data show that DHMEQ is a unique inhibitor of NF-kB that acts at the level of the nuclear translocation. It may be useful as an anti-inflammatory and anticancer agent.

Keywords: Apoptosis, DHMEQ, COS-1 Cells, NF-kB, Jurkat Cells

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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