Editors' ChoiceReceptor crosstalk

Glucocorticoid Receptor Sequesters p53

Science's STKE  21 Nov 2000:
Vol. 2000, Issue 59, pp. tw4
DOI: 10.1126/stke.2000.59.tw4

The tumor suppressor protein p53 can associate with the glucocorticoid receptor (GR) in vitro, and each protein is able to modulate the transcriptional activity of the other. Sengupta et al. extend these findings in vivo and suggest a mechanism for transcriptional attenuation. In cells transfected with GR, treatment with dexamethasone (Dex) inhibited p53-directed apoptosis and cell-cycle arrest. p53 and GR cotransfected cells revealed cytoplasmic staining for GR and diffuse nuclear and cytoplasmic staining for p53. However, in the presence of dexamethasone, overexpressed p53 and GR localized almost exclusively to the cytoplasm. The authors also demonstrated that, in neuroblastoma cell lines, GR associated with p53 in the absence of Dex; however, treatment with GR antagonists released p53 to the nucleus where it mediated the expression of several cell cycle-arrest genes, including Bax and p21, and reduced cell proliferation. Thus, aberrant cytosolic sequestration of wild-type p53 may contribute to disease states, and these results suggest that chemotherapeutic GR antagonists may function by liberating p53 from sequestration in the cytoplasm.

Sengupta, S., Vonesch, J.-L., Waltzinger, C., Zheng, H., and Wasylyk, B. (2000) Negative cross-talk between p53 and the glucocorticoid receptor and its role in neuroblastoma cells. EMBO J. 19: 6051-6064. [Abstract] [Full Text]