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Glucocorticoids antagonize Ap-1 by inhibiting the activation/phosphorylation of Jnk without affecting its subcellular distribution

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dc.creator González, María Victoria
dc.creator Jiménez, Benilde
dc.creator Berciano, María T.
dc.creator González-Sancho, José Manuel
dc.creator Caelles, Carme
dc.creator Lafarga, Miguel
dc.creator Muñoz Terol, Alberto
dc.date 2008-06-26T10:00:59Z
dc.date 2008-06-26T10:00:59Z
dc.date 2000-09-04
dc.date.accessioned 2017-01-31T01:55:47Z
dc.date.available 2017-01-31T01:55:47Z
dc.identifier Journal of Cell Biology 150(5): 1199–1208 (2000)
dc.identifier 0021-9525
dc.identifier http://hdl.handle.net/10261/5362
dc.identifier 10.1083/jcb.150.5.1199
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5362
dc.description 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.
dc.description This work was supported by grants from the Plan Nacional de Investigación y Desarrollo (SAF98-0060, 1FD97-0281-CO2-01), Comisión Interministerial de Ciencia y Tecnología, and Plan General de Conocimiento (PM96-0035), Ministerio de Educación y Cultura of Spain.
dc.description Peer reviewed
dc.format 473211 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.relation http://dx.doi.org/10.1083/jcb.150.5.1199
dc.rights openAccess
dc.subject Dexamethasone
dc.subject Activating protein-1
dc.subject Tumor necrosis factor α
dc.subject c-Jun NH2-terminal kinase
dc.subject Nuclear translocation
dc.title Glucocorticoids antagonize Ap-1 by inhibiting the activation/phosphorylation of Jnk without affecting its subcellular distribution
dc.type Artículo

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