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EMBO J. 2000 Nov 15;19(22):6051-64.

Negative cross-talk between p53 and the glucocorticoid receptor and its role in neuroblastoma cells.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, BP 163, 67404 Illkirch cedex, France.

Abstract

The tumour suppressor p53 and the glucocorticoid receptor (GR) respond to different types of stress. We found that dexamethasone-activated endogenous and exogenous GR inhibit p53-dependent functions, including transactivation, up- (Bax and p21(WAF1/CIP1)) and down- (Bcl2) regulation of endogenous genes, cell cycle arrest and apoptosis. GR forms a complex with p53 in vivo, resulting in cytoplasmic sequestration of both p53 and GR. In neuroblastoma (NB) cells, cytoplasmic retention and inactivation of wild-type p53 involves GR. p53 and GR form a complex that is dissociated by GR antagonists, resulting in accumulation of p53 in the nucleus, activation of p53-responsive genes, growth arrest and apoptosis. These results suggest that molecules that efficiently disrupt GR-p53 interactions would have a therapeutic potential for the treatment of neuroblastoma and perhaps other diseases in which p53 is sequestered by GR.

PMID:
11080152
PMCID:
PMC305812
DOI:
10.1093/emboj/19.22.6051
[Indexed for MEDLINE]
Free PMC Article

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