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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Autores principales: Josefine Stockert, Alexander Wolf, Kerstin Kaddatz, Evelyn Schnitzer, Florian Finkernagel, Wolfgang Meissner, Sabine Müller-Brüsselbach, Michael Kracht, Rolf Müller
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/6445710e006344f286931b2bb1cefae9
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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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