Regulation of tumour necrosis factor α mRNA stability by the mitogen-activated protein kinase p38 signalling cascade

The translation of tumour necrosis factor alpha (TNF alpha) mRNA is regulated by the stress-activated protein kinase p38, which also controls the stability of several pro-inflammatory mRNAs. The regulation of TNF alpha gene expression in a mouse macrophage cell line RAW264.7 was re-examined using an inhibitor of stress-activated protein kinases. Stimulation of these cells with bacterial lipopolysaccharide resulted in stabilisation of TNF alpha mRNA, which was reversed by specific inhibition of p38, An adenosine/uridine-rich element from the TNF alpha 3' untranslated region conferred p38-sensitive decay in a tetracycline-regulated mRNA stability assay. Therefore the p38 pathway also controls TNF alpha mRNA turnover. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.