Phosphorylation of PPARgamma via active ERK1/2 leads to its physical association with p65 and inhibition of NF-kappabeta
| Autor: | Fei, Chen, Muchun, Wang, J Patrick, O'Connor, Mai, He, Tushar, Tripathi, Lawrence E, Harrison |
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| Rok vydání: | 2003 |
| Předmět: |
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3 MAP Kinase Signaling System NF-kappa B Transcription Factor RelA Receptors Cytoplasmic and Nuclear Apoptosis Electrophoretic Mobility Shift Assay DNA Cell Line Tumor Humans Thiazolidinediones Mitogen-Activated Protein Kinases Phosphorylation Protein Binding Transcription Factors |
| Zdroj: | Journal of cellular biochemistry. 90(4) |
| ISSN: | 0730-2312 |
| Popis: | Peroxisome proliferator-activated receptors (PPAR) are novel nuclear receptors and PPARgamma ligands have been shown to produce pro-apoptotic effects in many cancer cell types, including colon cancer. PPARgamma ligands exert their effect through PPARgamma-dependent (genomic) and PPARgamma-independent (non-genomic) mechanisms. Recent evidence suggests that PPARgamma ligands exert their pro-apoptotic effects in part by directly antagonizing the NF-kappabeta pathway as well as through activation of the MAP kinase pathway. In this report, we have demonstrated that ciglitazone, a member of the thiazoldinedione class of PPARgamma ligands induces HT-29 colon cancer cells to undergo apoptosis and prior to apoptosis, ciglitazone exposure results in a transient phosphorylation of PPARgamma. This phosphorylation of PPARgamma was mediated through the ciglitazone-induced activation of Erk1/2. PPARgamma phosphorylation affected the genomic pathway by being inhibitory to PPARgamma-DNA binding and PPRE transcriptional activity, as well as the non-genomic pathway by increasing the physical interaction of PPARgamma with p65, leading to the inhibition of NF-kappabeta. Ciglitazone induced phosphorylation of PPARgamma through the MAP kinase pathway provides a potential regulatory mechanism for PPARgamma's physical interaction with p65, leading to inhibition of NF-kappabeta and subsequent apoptosis. |
| Databáze: | OpenAIRE |
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