Skip to Main content Skip to Navigation
Journal articles

Differential regulation of estrogen receptor alpha turnover and transactivation by Mdm2 and stress-inducing agents.

Abstract : In mammalian cells, the level of estrogen receptor alpha (ERalpha) is rapidly decreased upon estrogen treatment, and this regulation involves proteasome degradation. Using different approaches, we showed that the Mdm2 oncogenic ubiquitin-ligase directly interacts with ERalpha in a ternary complex with p53 and is involved in the regulation of ERalpha turnover (both in the absence or presence of estrogens). Several lines of evidence indicated that this effect of Mdm2 required its ubiquitin-ligase activity and involved the ubiquitin/proteasome pathway. Moreover, in MCF-7 human breast cancer cells, various p53-inducing agents (such as UV irradiation) or treatment with RITA (which inhibits the interaction of p53 with Mdm2) stabilized ERalpha and abolished its 17beta-estradiol-dependent turnover. Interestingly, our data indicated that ligand-dependent receptor turnover was not required for efficient transactivation. Altogether, our results indicate that the Mdm2 oncoprotein and stress-inducing agents complexly and differentially regulate ERalpha stability and transcriptional activity in human cancer cells.
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00157234
Contributor : Yves Le Ster <>
Submitted on : Tuesday, September 9, 2008 - 4:29:26 PM
Last modification on : Tuesday, November 24, 2020 - 9:12:02 AM
Long-term archiving on: : Thursday, April 8, 2010 - 5:56:39 PM

Identifiers

Collections

Citation

Vanessa Duong, Nathalie Boulle, Sylvain Daujat, Jérôme Chauvet, Sandrine Bonnet, et al.. Differential regulation of estrogen receptor alpha turnover and transactivation by Mdm2 and stress-inducing agents.. Cancer Research, American Association for Cancer Research, 2007, 67 (11), pp.5513-21. ⟨10.1158/0008-5472.CAN-07-0967⟩. ⟨inserm-00157234⟩

Share

Metrics

Record views

272

Files downloads

434