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Molecular and Cellular Biology, May 2005, p. 3421-3430, Vol. 25, No. 9
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.9.3421-3430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SPBP Is a Phosphoserine-Specific Repressor of Estrogen Receptor {alpha}

Valentina Gburcik,1 Nathalie Bot,1 Marcello Maggiolini,2 and Didier Picard1*

Département de Biologie Cellulaire, Université de Genève, Sciences III, Geneva, Switzerland,1 Department of Pharmaco-Biology, University of Calabria, Rende (CS), Italy2

Received 14 December 2004/ Returned for modification 19 January 2005/ Accepted 9 February 2005

Multiple signaling pathways stimulate the activity of estrogen receptor {alpha} (ER{alpha}) by direct phosphorylation within its N-terminal activation function 1 (AF1). How phosphorylation affects AF1 activity remains poorly understood. We performed a phage display screen for human proteins that are exclusively recruited to the phosphorylated form of AF1 and found the stromelysin-1 platelet-derived growth factor-responsive element-binding protein (SPBP). In a purified system, SPBP bound only the in vitro-phosphorylated form of the ER{alpha} AF1 or the phosphoserine mimic S118E, and the interaction domain could be mapped to a 42-amino-acid fragment of SPBP. In cells, SPBP preferentially interacted with liganded and phosphorylated ER{alpha}. Functionally, SPBP behaved as a repressor of activated ER{alpha}, which extends its previously demonstrated roles as a DNA binding transactivation factor and coactivator of other transcription factors. By targeting the phosphorylated form of AF1, SPBP may contribute to attenuating and fine-tuning ER{alpha} activity. A functional consequence is that SPBP inhibits the proliferation of ER{alpha}-dependent but not ER{alpha}-independent breast cancer cell lines, mirroring a reported negative correlation with the ER{alpha} status of breast tumors.

* Corresponding author. Mailing address: Department of Cell Biology, Sciences III, University of Geneva, 30 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland. Phone: 41 22 379 6813. Fax: 41 22 379 6928. E-mail: Picard{at}cellbio.unige.ch.

Molecular and Cellular Biology, May 2005, p. 3421-3430, Vol. 25, No. 9
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.9.3421-3430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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