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FEBS Lett. 2000 Oct 13;483(1):57-61.

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

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Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, Hammersmith, W6 8LH, London, UK.


The translation of tumour necrosis factor alpha (TNFalpha) mRNA is regulated by the stress-activated protein kinase p38, which also controls the stability of several pro-inflammatory mRNAs. The regulation of TNFalpha 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 TNFalpha mRNA, which was reversed by specific inhibition of p38. An adenosine/uridine-rich element from the TNFalpha 3' untranslated region conferred p38-sensitive decay in a tetracycline-regulated mRNA stability assay. Therefore the p38 pathway also controls TNFalpha mRNA turnover.

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