Open Access

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

  • Authors:
    • Shinya Mitsuhashi
    • Hiroshi Shima
    • Ying Li
    • Nobuhiro Tanuma
    • Takashi Okamoto
    • Kunimi Kikuchi
    • Makoto Ubukata
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/ijo_00000091
  • Pages: 1027-1035
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Abstract

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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Journal Cover

November 2008
Volume 33 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Mitsuhashi S, Shima H, Li Y, Tanuma N, Okamoto T, Kikuchi K and Ubukata M: Tautomycetin suppresses the TNFα/NF-κB pathway via inhibition of IKK activation. Int J Oncol 33: 1027-1035, 2008.
APA
Mitsuhashi, S., Shima, H., Li, Y., Tanuma, N., Okamoto, T., Kikuchi, K., & Ubukata, M. (2008). Tautomycetin suppresses the TNFα/NF-κB pathway via inhibition of IKK activation. International Journal of Oncology, 33, 1027-1035. https://doi.org/10.3892/ijo_00000091
MLA
Mitsuhashi, S., Shima, H., Li, Y., Tanuma, N., Okamoto, T., Kikuchi, K., Ubukata, M."Tautomycetin suppresses the TNFα/NF-κB pathway via inhibition of IKK activation". International Journal of Oncology 33.5 (2008): 1027-1035.
Chicago
Mitsuhashi, S., Shima, H., Li, Y., Tanuma, N., Okamoto, T., Kikuchi, K., Ubukata, M."Tautomycetin suppresses the TNFα/NF-κB pathway via inhibition of IKK activation". International Journal of Oncology 33, no. 5 (2008): 1027-1035. https://doi.org/10.3892/ijo_00000091