Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways

Stephen Safe, Kyoungkim Kim

Research output: Contribution to journalReview articlepeer-review

274 Scopus citations


17β-Estradiol binds to the estrogen receptor (ER) to activate gene expression or repression and this involves both genomic (nuclear) and non-genomic (extranuclear) pathways. Genomic pathways include the classical interactions of ligand-bound ER dimers with estrogen-responsive elements in target gene promoters. ER-dependent activation of gene expression also involves DNA-bound ER that subsequently interacts with other DNA-bound transcriptions factors and direct ER-transcription factor (protein-protein) interactions where ER does not bind promoter DNA. Ligand-induced activation of ER/specificity protein (Sp) and ER/activating protein-1 [(AP-1); consisting of jun/fos] complexes are important pathways for modulating expression of a large number of genes. This review summarizes some of the characteristics of ER/Sp- and ER/AP-1-mediated transactivation, which are dependent on ligand structure, cell context, ER-subtype (ERα and ERβ), and Sp protein (SP1, SP3, and SP4) and demonstrates that this non-classical genomic pathway is also functional in vivo.

Original languageEnglish (US)
Pages (from-to)263-275
Number of pages13
JournalJournal of Molecular Endocrinology
Issue number5-6
StatePublished - Nov 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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