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Title: Glucocorticoids antagonize AP-1 inhibiting the activation/phosphorylation of JNK without affecting its subcellular distribution
Author: González, María Victoria
Jiménez, Benilde
Berciano, María T.
González Sancho, José Manuel
Caelles Franch, Carme
Lafarga, Miguel
Muñoz, Alberto
Keywords: Glucocorticoides
Interacció cel·lular
Cell interaction
Issue Date: 4-Sep-2000
Publisher: Rockefeller University Press
Abstract: The immunosuppressive and antiinflammatory actions of glucocorticoid hormones are mediated by their transrepression of activating protein-1 (AP-1) and nuclear factor-kappa B (NFκB) transcription factors. Inhibition of the c-Jun NH2-terminal kinase (JNK) signaling pathway, the main mediator of AP-1 activation, has been described in extracts of hormone-treated cells. Here, we show by confocal laser microscopy, enzymatic assays, and immunoblotting that the synthetic glucocorticoid dexamethasone inhibited tumor necrosis factor α (TNF-α)–induced phosphorylation and activation of JNK in the cytoplasm and nucleus of intact HeLa cells. As a result, c-Jun NH2-terminal domain phosphorylation and induction were impaired. Dexamethasone did not block the TNF-α–induced JNK nuclear translocation, but rather induced, per se, nuclear accumulation of the enzyme. Consistently with previous findings, a glucocorticoid receptor mutant (GRdim), which is deficient in dimerization, DNA binding, and transactivation, but retains AP-1 transrepressing activity, was as efficient as wild-type GR in mediating the same effects of dexamethasone on JNK in transfected Cos-7 cells. Our results show that glucocorticoids antagonize the TNF-α–induced activation of AP-1 by causing the accumulation of inactive JNK without affecting its subcellular distribution.
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It is part of: Journal of Cell Biology, 2000, vol. 150, núm. 5, p. 1199-1208
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ISSN: 0021-9525
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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