Open AccessRegulation of TAK1/TAB1-Mediated IL-1β Signaling by Cytoplasmic PPARβ/δ
Author(s) -
Josefine Stockert,
Alexander Wolf,
Kerstin Kaddatz,
Evelyn Schnitzer,
Florian Finkernagel,
Wolfgang Meißner,
Sabine MüllerBrüsselbach,
Michael Kracht,
Rolf Müller
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0063011
Subject(s) - peroxisome proliferator activated receptor , hsp27 , microbiology and biotechnology , gene silencing , receptor , biology , signal transduction , effector , cytoplasm , heat shock protein , gene , biochemistry , hsp70
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.