title: Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ.
abstract: 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.
authors: Institute of Molecular Biology and Tumor Research-IMT, Philipps University, Marburg, Germany.
authors: Josefine
authors: J
authors: Stockert
authors: Alexander
authors: A
authors: Wolf
authors: Kerstin
authors: K
authors: Kaddatz
authors: Evelyn
authors: E
authors: Schnitzer
authors: Florian
authors: F
authors: Finkernagel
authors: Wolfgang
authors: W
authors: Meissner
authors: Sabine
authors: S
authors: Müller-Brüsselbach
authors: Michael
authors: M
authors: Kracht
authors: Rolf
authors: R
authors: Müller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D055551:HSP27 Heat-Shock Proteins; D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases; D047494:PPAR delta; D048068:PPAR-beta; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7; C486300:TAB1 protein, human
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