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This version published online on June 16, 2005
Molecular Endocrinology, doi:10.1210/me.2005-0042
A more recent version of this article appeared on November 1, 2005
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Submitted on January 17, 2005
Accepted on June 10, 2005

SUMOylation of the Estrogen receptor {alpha} hinge region by SUMO-E3 ligases PIAS1 and PIAS3 regulates ER{alpha} transcriptional activity

Stephanie Sentis, Murielle Le Romancer, Claire Bianchin, Marie-Claude Rostan, and Laura Corbo*

INSERM Unit 590, Centre Léon Bérard, 69373 Lyon Cedex 08, France

* To whom correspondence should be addressed. E-mail: corbo{at}lyon.fnclcc.fr.

The steroid hormone 17{beta}-estradiol (estrogen) plays a significant role in the normal physiology of the mammary gland and breast cancer development primarily through binding to its receptor, the estrogen receptor {alpha} (ER{alpha}). ER{alpha} is a nuclear transcription factor undergoing different types of post-translational modifications, i.e. phosphorylation, acetylation and ubiquitination, which regulate its transcriptional activation and/or stability. Here we identify ER{alpha} as a new target for SUMO-1 modification in intact cells and in vitro. Moreover, ER{alpha} sumoylation occurs strictly in the presence of hormone. SUMO-1 appears to regulate ER{alpha}-dependent transcription. Using a series of mutants, we demonstrated that ER{alpha} is sumoylated at conserved lysine residues within the hinge region. Mutations that prevented SUMO modification impaired ER{alpha}-induced transcription without influencing ER{alpha} cellular localization. In addition to identifying PIAS1 and PIAS3 as E3 ligases for ER{alpha}, we also found that PIAS1 and PIAS3, as well as Ubc9, modulated ER{alpha}-dependent transcription independently from their SUMO-1 conjugation activity. These findings identify sumoylation as a new mechanism modulating ER{alpha}-dependent cellular response and provide a link between the SUMO and estrogen pathways.
Key words: ER{alpha} • SUMO-1 • PIAS1 • PIAS3 • Ubc9

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα
Coregulators:   PIAS1  |  PIAS3
Ligands:   17β-Estradiol  |  4-Hydroxytamoxifen



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