Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain

Mari Luz Acevedo, Kathleen C. Lee, Joshua D. Stender, Benita S Katzenellenbogen, W. Lee Kraus

Research output: Contribution to journalArticle

Abstract

How nuclear receptors (NRs) coordinate the sequential, ligand-dependent recruitment of multiple coactivator complexes (e.g., SRC complexes and Mediator) that share similar receptor binding determinants is unclear. We show that although the receptor binding subunits of these complexes (i.e., SRCs and Med220, respectively) share overlapping binding sites on estrogen receptor α (ERα), information contained in the receptor-coactivator interface allows the receptor to distinguish between them. In support of this conclusion, we have identified an ERα AF-2 point mutant (L540Q) that selectively binds and recruits Med220, but not SRCs, both in vitro and in vivo. In cells expressing this mutant, the recruitment of Med220 to the pS2 promoter is delayed, and the expression of the vast majority of estrogen target genes is impaired, suggesting a nearly global functional interdependence of these coactivators. Collectively, our results suggest that "facilitated recruitment," rather than competition, drives the sequential recruitment of SRC complexes and Mediator by NRs.

Original languageEnglish (US)
Pages (from-to)725-738
Number of pages14
JournalMolecular cell
Volume13
Issue number5
DOIs
StatePublished - Mar 5 2004

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Mediator Complex
Cytoplasmic and Nuclear Receptors
Furylfuramide
Ligands
Estrogen Receptor beta
Estrogen Receptors
Estrogens
Binding Sites
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. / Acevedo, Mari Luz; Lee, Kathleen C.; Stender, Joshua D.; Katzenellenbogen, Benita S; Kraus, W. Lee.

In: Molecular cell, Vol. 13, No. 5, 05.03.2004, p. 725-738.

Research output: Contribution to journalArticle

Acevedo, Mari Luz ; Lee, Kathleen C. ; Stender, Joshua D. ; Katzenellenbogen, Benita S ; Kraus, W. Lee. / Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. In: Molecular cell. 2004 ; Vol. 13, No. 5. pp. 725-738.
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