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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5362| Title: | Glucocorticoids antagonize Ap-1 by inhibiting the activation/phosphorylation of Jnk without affecting its subcellular distribution |
| Keywords: | Dexamethasone Activating protein-1 Tumor necrosis factor α c-Jun NH2-terminal kinase Nuclear translocation |
| Publisher: | Rockefeller University Press |
| 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. 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. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5362 |
| Other Identifiers: | Journal of Cell Biology 150(5): 1199–1208 (2000) 0021-9525 http://hdl.handle.net/10261/5362 10.1083/jcb.150.5.1199 |
| Appears in Collections: | Digital Csic |
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