HDAC Activity Is Required for p65/RelA-Dependent Repression of PPARδ-Mediated Transactivation in Human Keratinocytes
| Autor: | Jens S. Andersen, Esben N. Flindt, Karsten Kristiansen, Lene Aarenstrup, Morten Kirkegaard, Kristian Otkjaer |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Keratinocytes Transcriptional Activation Repressor Histone Deacetylase 1 Dermatology Biology Biochemistry Histone Deacetylases Transactivation medicine Humans Immunoprecipitation PPAR delta Molecular Biology Psychological repression Cells Cultured Transcription Factor RelA Cell Differentiation Cell Biology HDAC1 Protein Structure Tertiary medicine.anatomical_structure Histone Epidermal Cells biology.protein Cancer research Peroxisome proliferator-activated receptor delta Histone deacetylase Epidermis Keratinocyte |
| Zdroj: | Aarenstrup, L, Flindt, E N, Otkjaer, K, Kirkegaard, M, Andersen, J S & Kristiansen, K 2008, ' HDAC Activity Is Required for p65/RelA-Dependent Repression of PPARdelta-Mediated Transactivation in Human Keratinocytes ', Journal of Investigative Dermatology, vol. 128, pp. 1095-1106 . https://doi.org/10.1038/sj.jid.5701146 Aarenstrup, L, Flindt, E N, Otkjaer, K, Kirkegaard, M, Andersen, J S & Kristiansen, K 2007, ' HDAC activity is required for p65/RelA-dependent repression of PPARdelta-mediated transactivation in human keratinocytes ', Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1095-106 . https://doi.org/10.1038/sj.jid.5701146 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5701146 |
| Popis: | Peroxisome proliferator-activated receptors (PPARs) play a key role in differentiation, inflammation, migration, and survival of epidermal keratinocytes. The NF-kappaB has long been known to play pivotal roles in immune and inflammatory responses, and furthermore NF-kappaB has been implicated in the regulation of epidermal homeostasis. Recent studies have established that p65/RelA is a potent repressor of PPARdelta-mediated transactivation in human keratinocytes. In this article we further investigate the molecular mechanisms dictating the NF-kappaB-dependent repression of PPARdelta in human keratinocytes. We demonstrate that repression is unique to p65/RelA, as no other member of the NF-kappaB family had an impact on PPARdelta-mediated transactivation. Interestingly, our results show that p65/RelA only represses PPARdelta-dependent transactivation when PPARdelta is bound to DNA via its DNA-binding domain. We show that repression is sensitive to inhibition of histone deacetylases (HDACs) by tricostatin A (TSA), suggesting that HDAC activity is indispensable for p65/RelA-mediated repression. Accordingly, we demonstrate that a ternary complex consisting of PPARdelta, p65/RelA, and HDAC1 is formed in vivo. Finally, we demonstrate that TSA relieves tumor necrosis factor-alpha (TNFalpha)-induced repression of PPARdelta-mediated transactivation of the PPARdelta target gene adipose differentiation-related protein (ADRP) indicating that cross-talk between PPARdelta and NF-kappaB is of biological significance in human keratinocytes.Journal of Investigative Dermatology advance online publication, 22 November 2007; doi:10.1038/sj.jid.5701146. |
| Databáze: | OpenAIRE |
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