Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ.
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 interf...
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oai:doaj.org-article:6445710e006344f286931b2bb1cefae92021-11-18T07:47:20ZRegulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ.1932-620310.1371/journal.pone.0063011https://doaj.org/article/6445710e006344f286931b2bb1cefae92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23646170/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Josefine StockertAlexander WolfKerstin KaddatzEvelyn SchnitzerFlorian FinkernagelWolfgang MeissnerSabine Müller-BrüsselbachMichael KrachtRolf MüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e63011 (2013) |
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Medicine R Science Q Josefine Stockert Alexander Wolf Kerstin Kaddatz Evelyn Schnitzer Florian Finkernagel Wolfgang Meissner Sabine Müller-Brüsselbach Michael Kracht Rolf Müller Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
description |
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. |
format |
article |
author |
Josefine Stockert Alexander Wolf Kerstin Kaddatz Evelyn Schnitzer Florian Finkernagel Wolfgang Meissner Sabine Müller-Brüsselbach Michael Kracht Rolf Müller |
author_facet |
Josefine Stockert Alexander Wolf Kerstin Kaddatz Evelyn Schnitzer Florian Finkernagel Wolfgang Meissner Sabine Müller-Brüsselbach Michael Kracht Rolf Müller |
author_sort |
Josefine Stockert |
title |
Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
title_short |
Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
title_full |
Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
title_fullStr |
Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
title_full_unstemmed |
Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ. |
title_sort |
regulation of tak1/tab1-mediated il-1β signaling by cytoplasmic pparβ/δ. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/6445710e006344f286931b2bb1cefae9 |
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