Coactivation of estrogen receptor α (ERα)/Sp1 by vitamin D receptor interacting protein 150 (DRIP150)

Jeongeun Lee, Stephen Safe

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Vitamin D receptor interacting protein (DRIP150) coactivates estrogen receptor α (ERα)-mediated transactivation in breast cancer cell lines transfected with a construct (pERE3) containing three estrogen responsive elements (EREs). In this study, we show that DRIP150 also coactivates ERα/Sp1-mediated transactivation in ZR-75, MCF-7, and MDA-MB-231 breast cancer cells transfected with a construct (pSp13) containing three consensus GC-rich motifs. Studies on coactivation of wild-type and variant ERα/Sp1 by DRIP150 indicates that the DNA-binding domain and helix 12 in the ligand binding domain of ERα are required and the coactivation response is squelched by overexpressing an NR-box peptide that contains two LXXLL motifs from GRIP2. In contrast, coactivation of ERα/Sp1 by wild-type and mutant DRIP150 expression plasmids show that coactivation of ERα/Sp1 by DRIP150 is independent of the NR-boxes. Deletion analysis of DRIP150 demonstrates that coactivation requires an α-helical NIFSEVRVYN (amino acids 795-804) motif within 23 amino acid sequence (789-811) in the central region of DRIP150 and similar results were obtained for coactivation of ERα by DRIP150. Thus, although different domains of ERα are required for hormone-dependent activation of ERα and ERα/Sp1, coactivation of these transcription factors by DRIP150 requires the α-helical amino acids 795-804. This is the first report of a coactivator that enhances ERα/Sp1-mediated transactivation in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume461
Issue number2
DOIs
StatePublished - May 15 2007

Keywords

  • Coactivation
  • DRIP150
  • ERα/Sp1
  • NR box-independent
  • ZR-75 cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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