Caveolin-1 potentiates estrogen receptor α (ERα) signaling. Caveolin-1 drives ligand-independent nuclear translocation and activation of ERα

Amnon Schlegel, Chenguang Wang, Benita S. Katzenellenbogen, Richard G. Pestell, Michael P. Lisanti

Research output: Contribution to journalArticle

Abstract

Estrogen receptor α (ERα) is a soluble protein that mediates the effects of the gonadal estrogens such as 17β-estradiol. Upon ligand binding, a cytoplasmic pool of ERα translocates to the nucleus, where it acts as a transcription factor, driving the expression of genes that contain estrogen- response elements. The activity of ERα is regulated by a number of proteins, including cytosolic chaperones and nuclear cofactors. Here, we show that caveolin-1 potentiates ERα-mediated signal transduction. Coexpression of caveolin-1 and ERα resulted in ligand-independent translocation of ERα to the nucleus as shown by both cell fractionation and immunofluorescence microscopic studies. Similarly, caveolin-1 augmented both ligand-independent and ligand-dependent ERα signaling as measured using a estrogen-response element-based luciferase reporter assay. Caveolin-1-mediated activation of ERα was sensitive to a well known ER antagonist, 4-hydroxytamoxifen. However, much higher concentrations of tamoxifen were required to mediate inhibition in the presence of caveolin-1. Interestingly, caveolin-1 expression also synergized with a constitutively active, ligand-independent ERα mutant, dramatically illustrating the potent stimulatory effect of caveolin-1 in this receptor system. Taken together, our results identify caveolin-1 as a new positive regulator of ERα signal transduction.

Original languageEnglish (US)
Pages (from-to)33551-33556
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number47
DOIs
StatePublished - Nov 19 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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