| Autor: |
Kenneth T Farabaugh, Dawid Krokowski, Bo-Jhih Guan, Zhaofeng Gao, Xing-Huang Gao, Jing Wu, Raul Jobava, Greeshma Ray, Tristan J de Jesus, Massimiliano G Bianchi, Evelyn Chukwurah, Ovidio Bussolati, Michael Kilberg, David A Buchner, Ganes C Sen, Calvin Cotton, Christine McDonald, Michelle Longworth, Parameswaran Ramakrishnan, Maria Hatzoglou |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 9 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.52241 |
| Popis: |
The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker of the termination of adaptation and initiation of inflammation in Mus musculus embryonic fibroblasts. We found that high stress-induced PACT-PKR activation inhibits the interaction between NF-κB c-Rel and TonEBP essential for the increased expression of TonEBP-dependent osmoprotective genes. This resulted in enhanced formation of TonEBP/NF-κB p65 complexes and enhanced proinflammatory gene expression. These data demonstrate a novel role of c-Rel in the adaptive response to hyperosmotic stress, which is inhibited via a PACT/PKR-dependent dimer redistribution of the Rel family transcription factors. Our results suggest that inhibiting PACT-PKR signaling may prove a novel target for alleviating stress-induced inflammatory diseases. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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