| 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 |
|