Identification of the MLL2 complex as a coactivator for estrogen receptor α

Rigen Mo, Sambasiva M. Rao, Yi Jun Zhu*

*Corresponding author for this work

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

A novel estrogen receptor (ER)α coactivator complex, the MLL2 complex, which consists of MLL2, ASH2, RBQ3, and WDR5, was identified. ERα directly binds to the MLL2 complex through two LXXLL motifs in a region of MLL2 near the C terminus in a ligand-dependent manner. Disrupting the interaction between ERα and the MLL2 complex with small interfering RNAs specific against MLL2 or an MLL2 fragment representing the interacting region with ERα significantly inhibited the ERα transcription activity. The MLL2 complex was recruited on promoters of ERα target genes along with ERα upon estrogen stimulation. Inhibition of MLL2 expression decreased the estrogen-induced expression of ERα target genes cathepsinDand to a lesser extent pS2. In addition, MCF-7 cell growth was also inhibited by the depletion of MLL2. These results demonstrate that the ERα signaling pathway is critically dependent on its direct interaction with the MLL2 complex and suggest a central role for the MLL2 complex in the growth of ERα-positive cancer cells.

Original languageEnglish (US)
Pages (from-to)15714-15720
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number23
DOIs
StatePublished - Jun 9 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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