Tautomycetin suppresses the TNFalpha/NF-kappaB pathway via inhibition of IKK activation.

TNFalpha activated NF-kappaB 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-kappaB among the three TNFalpha effectors (NF-kappaB, JNK and caspase). TC inhibited T-loop phosphorylation of IKKalpha and IKKbeta, thereby preventing ...
degradation of the NF-kappaB inhibitor, IkappaBalpha. Co-immunoprecipitation experiments revealed that the catalytic subunit of PP1 (PP1C) was involved in the IKK complex. Pull-down analysis using recombinant GST-TNFalpha, 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 TNFalpha-induced NF-kappaB pathway at the level of IKK activation. Thus, TC might be used therapeutically to suppress the TNFalpha/NF-kappaB pathway.
Mesh Terms:
Animals, COS Cells, Cercopithecus aethiops, Dose-Response Relationship, Drug, Furans, HeLa Cells, Humans, I-kappa B Kinase, I-kappa B Proteins, Lipids, MAP Kinase Kinase Kinases, NF-kappa B, Protein Kinase Inhibitors, Protein Phosphatase 1, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, Type I, Recombinant Fusion Proteins, Recombinant Proteins, Signal Transduction, Time Factors, Transfection, Tumor Necrosis Factor-alpha
Int. J. Oncol.
Date: Nov. 01, 2008
Download Curated Data For This Publication
154764
Switch View:
  • Interactions 13