Krüppel-Associated Box-Associated Protein 1 Negatively Regulates TNF-α–Induced NF-κB Transcriptional Activity by Influencing the Interactions among STAT3, p300, and NF-κB/p65
| Autor: | Kenji Oritani, Asuka Sakauchi, Ryuta Muromoto, Yuichi Sekine, Osamu Ikeda, Tadashi Matsuda, Sumihito Togi, Shinya Kamitani, Misa Nakasuji |
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| Rok vydání: | 2011 |
| Předmět: |
STAT3 Transcription Factor
Chromatin Immunoprecipitation Transcription Genetic Blotting Western Immunology Gene Expression Enzyme-Linked Immunosorbent Assay Tripartite Motif-Containing Protein 28 Biology chemistry.chemical_compound Humans Immunoprecipitation Immunology and Allergy RNA Small Interfering STAT3 Transcription factor Regulation of gene expression Gene knockdown Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha NF-kappa B NF-κB Molecular biology Repressor Proteins IκBα Gene Expression Regulation Microscopy Fluorescence chemistry Acetylation biology.protein Phosphorylation E1A-Associated p300 Protein HeLa Cells Signal Transduction |
| Zdroj: | The Journal of Immunology. 187:2476-2483 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1003243 |
| Popis: | Krüppel-associated box-associated protein 1 (KAP1) is thought to act mainly as a scaffold for protein complexes, which together silence transcription by triggering the formation of heterochromatin. Using small interfering RNA-mediated KAP1 knockdown, we found that endogenous KAP1 negatively regulated TNF-α–induced IL-6 production in HeLa cells. KAP1 is likely to modulate the binding of NF-κB to the IL-6 promoter because KAP1 knockdown enhanced TNF-α–induced NF-κB-luciferase activity, but not IκBα degradation. Of importance, we found negative regulatory effects of KAP1 on the serine phosphorylation of STAT3, the acetylation of NF-κB/p65 by p300, and the nuclear localization of NF-κB/p65. In addition, KAP1 associated with NF-κB/p65 and inhibited the binding between NF-κB/p65 and p300. Thus, KAP1 is likely to negatively control the acetylation of NF-κB/p65, which is critical for its nuclear retention. Taken together, KAP1 modulated the acetylation of NF-κB/p65 by interfering with the interactions among STAT3, p300, and NF-κB/p65, resulting in reduced IL-6 production after TNF-α stimulation. Our findings that KAP1 directly interacts with transcriptional factors are new, and will inform further research to elucidate KAP1 function. |
| Databáze: | OpenAIRE |
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