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Tautomycetin suppresses the TNFα/NF-κB pathway via inhibition of IKK activation

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TNFα activated NF-κB and associated regulatory factors including IKK are strongly implicated in a variety of hematological and solid tumor malignancies. We show that tautomycetin (TC) specifically inhibits activation of NF-κB among the three TNFα effectors (NF-κB, JNK and caspase). TC inhibited T-loop phosphorylation of IKKα and IKKβ, thereby preventing degradation of the NF-κB inhibitor, IκBα. Co-immunoprecipitation experiments revealed that the catalytic subunit of PP1 (PP1C) was involved in the IKK complex. Pull-down analysis using recombinant GST-TNFα, showed that PP1C was recruited to TNFR1 together with IKK complex, RIP and TAK1 upon stimulus. These results suggest that the PP1 positively regulates the TNFα-induced NF-κB pathway at the level of IKK activation. Thus, TC might be used therapeutically to suppress the TNFα/NF-κB pathway.
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Document Type: Research Article

Affiliations: Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan

Publication date: November 1, 2008

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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