Kabouridis, PS; Hasan, M; Newson, J; Gilroy, DW; Lawrence, T; (2002) Inhibition of NF-kappa B activity by a membrane-transducing mutant of I kappa B alpha. J.Immunol. , 169 (5) 2587 - 2593.
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The transcription factor NF-kappaB is regulated by the IkappaB family of proteins. The nonphosphorylatable, nondegradable superrepressor IkappaBalpha (srIkappaBalpha) mutant is a potent inhibitor of NF-kappaB activity when expressed in cells. We generated a form of srIkappaBalpha in which its N terminus is fused to the protein transduction domain of HIV TAT (TAT-srIkappaBalpha). Purified TAT-srIkappaBalpha protein rapidly and efficiently entered HeLa or Jurkat T cells. TAT-srIkappaBalpha, when exogenously added to HeLa cells, inhibited in a dose-dependent manner TNF-alpha- or IL-1beta-induced NF-kappaB activation and binding of NF-kappaB to its consensus DNA sequence. TAT-srIkappaBalpha was coimmunoprecipitated with the p65 subunit of NF-kappaB, and this interaction was resistant to stimulation with IL-1beta. Therefore, TAT-srIkappaBalpha-mediated inhibition could result from its nonreversible binding and sequestration of endogenous NF-kappaB. In contrast, exogenously added TAT-srIkappaBalpha did not inhibit IL-1beta-induced activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, or p38 mitogen-activated protein kinases or the phosphorylation and degradation of endogenous IkappaBalpha. These results identify a novel way for direct regulation of NF-kappaB activity in diverse cell types that may be useful for therapeutic purposes
|Title:||Inhibition of NF-kappa B activity by a membrane-transducing mutant of I kappa B alpha|
|Additional information:||DA - 20020823IS - 0022-1767 (Print)LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tRN - 0 (DNA-Binding Proteins)RN - 0 (Gene Products, tat)RN - 0 (I-kappa B Proteins)RN - 0 (NF-kappa B)RN - 0 (Recombinant Fusion Proteins)RN - 0 (Repressor Proteins)RN - 0 (Transcription Factor RelA)RN - 139874-52-5 (NF-kappaB inhibitor alpha)RN - EC 126.96.36.199 (Mitogen-Activated Protein Kinases)SB - AIMSB - IM|
|Keywords:||Binding, Competitive, genetics, Biological Transport, Cell Membrane, metabolism, Consensus Sequence, DNA-Binding Proteins, antagonists & inhibitors, physiology, Gene Products, tat, Hela Cells, Humans, I-kappa B Proteins, Jurkat Cells, MAP Kinase Signaling System, Mitogen-Activated Protein Kinases, Mutation, NF-kappa B, Recombinant Fusion Proteins, Repressor Proteins, Transcription Factor RelA, Transcription, Genetic, Transduction, Genetic|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics|
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