دورية أكاديمية
The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-kappaB
| العنوان: | The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-kappaB |
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| المؤلفون: | Ziesché, Elisabeth, Kettner-Buhrow, Daniela, Weber, Axel, Wittwer, Tobias, Jurida, Liane, Soelch, Johanna, Müller, Helmut, Newel, Doris, Kronich, Petra, Schneider, Heike, Dittrich-Breiholz, Oliver, Bhaskara, Srividya, Hiebert, Scott W., Hottiger, Michael O., Li, Haiying, Burstein, Ezra, Schmitz, M. Lienhard, Kracht, Michael |
| سنة النشر: | 2022 |
| المجموعة: | Publication Server of the Justus-Liebig-University of Giessen |
| مصطلحات موضوعية: | histone deacetylase 3 (HDAC3), NF-kappaB p65, positive gen-regulation of IL-1, co-activator in inflammatory signaling pathways, ddc:610 |
| الوصف: | Histone deacetylase (HDAC) 3, as a cofactor in co-repressor complexes containing silencing mediator for retinoid or thyroid-hormone receptors (SMRT) and nuclear receptor co-repressor (N-CoR), has been shown to repress gene transcription in a variety of contexts. Here, we reveal a novel role for HDAC3 as a positive regulator of IL-1-induced gene expression. Various experimental approaches involving RNAi-mediated knockdown, conditional gene deletion or small molecule inhibitors indicate a positive role of HDAC3 for transcription of the majority of IL-1-induced human or murine genes. This effect was independent from the gene regulatory effects mediated by the broad-spectrum HDAC inhibitor trichostatin A (TSA) and thus suggests IL-1-specific functions for HDAC3. The stimulatory function of HDAC3 for inflammatory gene expression involves a mechanism that uses binding to NF-?B p65 and its deacetylation at various lysines. NF-?B p65-deficient cells stably reconstituted to express acetylation mimicking forms of p65 (p65 K/Q) had largely lost their potential to stimulate IL-1-triggered gene expression, implying that the co-activating property of HDAC3 involves the removal of inhibitory NF-?B p65 acetylations at K122, 123, 314 and 315. These data describe a novel function for HDAC3 as a co-activator in inflammatory signaling pathways and help to explain the anti-inflammatory effects frequently observed for HDAC inhibitors in (pre)clinical use. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-90755Test; https://jlupub.ub.uni-giessen.de//handle/jlupub/9664Test; http://dx.doi.org/10.22029/jlupub-9052Test |
| DOI: | 10.22029/jlupub-9052 |
| الإتاحة: | https://doi.org/10.22029/jlupub-9052Test http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-90755Test https://jlupub.ub.uni-giessen.de//handle/jlupub/9664Test |
| حقوق: | Namensnennung - Nicht-kommerziell - Keine Bearbeitung 3.0 International ; https://creativecommons.org/licenses/by-nc-nd/3.0Test/ |
| رقم الانضمام: | edsbas.7A4D830F |
| قاعدة البيانات: | BASE |
| DOI: | 10.22029/jlupub-9052 |
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