Estrogen receptor pathways to AP-1

Peter J. Kushner, David A. Agard, Geoffrey L. Greene, Thomas S. Scanlan, Andrew K. Shiau, Rosalie M. Uht, Paul Webb

Research output: Contribution to journalArticle

693 Scopus citations

Abstract

Estrogen receptor (ER) binds to estrogen response elements in target genes and recruits a coactivator complex of CBP-pl60 that mediates stimulation of transcription. ER also activates transcription at AP-1 sites that bind the Jun/Fos transcription factors, but not ER. We review the evidence regarding mechanisms whereby ER increases the activity of Jun/Fos and propose two pathways of ER action depending on the ER (α or β) and on the ligand. We propose that estrogen-ERα complexes use their activation functions (AF-1 and AF-2) to bind to the p 160 component of the coactivator complex recruited by Jun/Fos and trigger the coactivator to a higher state of activity. We propose that selective estrogen receptor modulator (SERM) complexes with ERβ and with truncated ERα derivatives use their DNA binding domain to titrate histone deacetylase (HDAC)-repressor complexes away from the Jun/Fos coactivator complex, thereby allowing unfettered activity of the coactivators. Finally, we consider the possible physiological significance of ER action at AP-1 sites.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume74
Issue number5
DOIs
StatePublished - Nov 30 2000

Keywords

  • Coactivator
  • Estrogen receptor
  • Transcription factors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Kushner, P. J., Agard, D. A., Greene, G. L., Scanlan, T. S., Shiau, A. K., Uht, R. M., & Webb, P. (2000). Estrogen receptor pathways to AP-1. Journal of Steroid Biochemistry and Molecular Biology, 74(5), 311-317. https://doi.org/10.1016/S0960-0760(00)00108-4