Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ
| Autor: | Alexander Wolf, Sabine Müller-Brüsselbach, Rolf Müller, Florian Finkernagel, Wolfgang Meissner, Evelyn Schnitzer, Kerstin Kaddatz, Josefine Stockert, Michael Kracht |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cytoplasm
Small interfering RNA Transcription Genetic Interleukin-1beta HSP27 Heat-Shock Proteins Molecular cell biology Transcriptional regulation Signaling in Cellular Processes PPAR delta Crosstalk Regulation of gene expression Multidisciplinary Protein Kinase Signaling Cascade Mechanisms of Signal Transduction Genomics Signaling in Selected Disciplines MAP Kinase Kinase Kinases Chromatin Signaling Cascades Nuclear Signaling Phosphorylation Medicine Peroxisome proliferator-activated receptor delta Signal transduction Research Article Signal Transduction Protein Binding Steroid hormone receptor Science DNA transcription Biology Immunological Signaling Humans Protein Interaction Domains and Motifs PPAR-beta Adaptor Proteins Signal Transducing Gene Expression Profiling Transcription Factor RelA Comparative Genomics Molecular biology IκBα Gene Expression Regulation Gene expression Transcriptional Signaling Nuclear Receptor Signaling Genome Expression Analysis HeLa Cells |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e63011 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The peroxisome proliferator-activated receptor subtypes PPARα, PPARβ/δ, PPARγ are members of the steroid hormone receptor superfamily with well-established functions in transcriptional regulation. Here, we describe an unexpected cytoplasmic function of PPARβ/δ. Silencing of PPARβ/δ expression interferes with the expression of a large subset of interleukin-1β (IL-1β)-induced target genes in HeLa cells, which is preceded by an inhibition of the IL-1β-induced phosphorylation of TAK1 and its downstream effectors, including the NFκBα inhibitor IκBα (NFKBIA) and the NFκBα subunit p65 (RELA). PPARβ/δ enhances the interaction between TAK1 and the small heat-shock protein HSP27, a known positive modulator of TAK1-mediated IL-1β signaling. Consistent with these findings, PPARβ/δ physically interacts with both the endogenous cytoplasmic TAK1/TAB1 complex and HSP27, and PPARβ/δ overexpression increases the TAK1-induced transcriptional activity of NFκB. These observations suggest that PPARβ/δ plays a role in the assembly of a cytoplasmic multi-protein complex containing TAK1, TAB1, HSP27 and PPARβ/δ, and thereby participates in the NFκB response to IL-1β. |
| Databáze: | OpenAIRE |
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