Involvement of ZIP/p62 in the regulation of PPARalpha transcriptional activity by p38-MAPK
| Autor: | Jean-Paul Pégorier, Cédric Le May, Claire Diradourian, Michèle Caüzac, Jean Girard, Anne-Françoise Burnol |
|---|---|
| Přispěvatelé: | unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Transcription
Genetic MAP Kinase Signaling System p38 mitogen-activated protein kinases Biology digestive system p38 Mitogen-Activated Protein Kinases 03 medical and health sciences chemistry.chemical_compound Enzyme activator 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Cell Line Tumor Chlorocebus aethiops Sequestosome-1 Protein [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Glucose homeostasis Animals PPAR alpha RNA Small Interfering Extracellular Signal-Regulated MAP Kinases Molecular Biology ComputingMilieux_MISCELLANEOUS Anisomycin Protein kinase C Heat-Shock Proteins Protein Kinase C 030304 developmental biology Nucleic Acid Synthesis Inhibitors 0303 health sciences Activator (genetics) food and beverages nutritional and metabolic diseases [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Cell Biology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Molecular biology Cyclic AMP-Dependent Protein Kinases Rats Enzyme Activation chemistry Nuclear receptor 030220 oncology & carcinogenesis COS Cells cardiovascular system Phosphorylation lipids (amino acids peptides and proteins) |
| Zdroj: | BBA-Biochimica et Biophysica Acta BBA-Biochimica et Biophysica Acta, Elsevier, 2008, 1781 (5), pp.239-244. ⟨10.1016/j.bbalip.2008.02.002⟩ |
| ISSN: | 0006-3002 |
| Popis: | The peroxisome proliferator-activated receptor alpha (PPARalpha) belongs to the nuclear receptor family and plays a central role in the regulation of lipid metabolism, glucose homeostasis and inflammatory processes. In addition to its ligand-induced activation, PPARalpha is regulated by phosphorylation via ERK-MAPK, PKA and PKC. In this study we examined the effect of p38-MAPK on PPARalpha transcriptional activity. In COS-7 cells, anisomycin, a p38 activator, induced a dose-dependent phosphorylation of PPARalpha and a 50% inhibition of its transcriptional activity. In H4IIE hepatoma cells, anisomycin-induced p38 phosphorylation decreased both endogenous and PPARalpha ligand-enhanced L-CPTI and ACO gene expression. Interestingly, PPARalpha/p38 interaction required the molecular adapter ZIP/p62. Reducing ZIP/p62 expression by siRNA, partially reversed the inhibitory effect of anisomycin on L-CPTI gene expression. In conclusion, we showed that p38 activation induced PPARalpha phosphorylation and inhibition of its transcriptional activity through a trimeric interaction between p38-MAPK, ZIP/p62 and PPARalpha. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|