en
Scientific article
English

SPBP is a phosphoserine-specific repressor of estrogen receptor alpha

Published inMolecular and cellular biology, vol. 25, no. 9, p. 3421-3430
Publication date2005
Abstract

Multiple signaling pathways stimulate the activity of estrogen receptor alpha (ERalpha) 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 ERalpha 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 ERalpha. Functionally, SPBP behaved as a repressor of activated ERalpha, 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 ERalpha activity. A functional consequence is that SPBP inhibits the proliferation of ERalpha-dependent but not ERalpha-independent breast cancer cell lines, mirroring a reported negative correlation with the ERalpha status of breast tumors.

Keywords
  • Amino Acid Sequence
  • Breast Neoplasms/genetics/metabolism
  • Cell Line
  • Cell Proliferation
  • Estrogen Receptor alpha/antagonists & inhibitors/genetics/metabolism
  • Female
  • Humans
  • Immunoprecipitation
  • Molecular Sequence Data
  • Mutation/genetics
  • Peptide Library
  • Phosphorylation
  • Phosphoserine/metabolism
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • RNA, Small Interfering/genetics
  • Repressor Proteins/genetics/metabolism/physiology
  • Response Elements/genetics
  • Transcription Factors/genetics/metabolism/physiology
Citation (ISO format)
GBURCIK, Valentina et al. SPBP is a phosphoserine-specific repressor of estrogen receptor alpha. In: Molecular and cellular biology, 2005, vol. 25, n° 9, p. 3421–3430. doi: 10.1128/MCB.25.9.3421-3430.2005
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Article (Published version)
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Identifiers
ISSN of the journal0270-7306
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