Cooperative coactivation of estrogen receptor α in ZR-75 human breast cancer cells by SNURF and TATA-binding protein

Bradley Saville, Hetti Poukka, Mark Wormke, Olli A. Jänne, Jorma J. Palvimo, Matthew Stoner, Ismael Samudio, Stephen Safe

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

SNURF is a small RING finger protein that binds the zinc finger region of steroid hormone receptors and enhances Sp1- and androgen receptor-mediated transcription in COS and CV-1 cells. In this study, we show that SNURF coactivates both wild-type estrogen receptor a (ERα) (4-fold)-and HE19 (ERα deletion of activation function 1 (AF1)) (210-fold)-mediated activation of an estrogen-responsive element promoter in ZR-75 cells. In mammalian two-hybrid assays in ZR-75 cells SNURF interactions were estrogen (E2)-dependent and were not observed with the antiestrogen ICI 182,780. ERα interacted with multiple regions of SNURF; SNURF interactions with ERα were dependent on AF2, and D538N, E542Q, and D545N mutations in helix 12 abrogated both SNURF-ERα binding and coactivation. Moreover, peptide fusion proteins that inhibit interactions between helix 12 of ERα with LXXLL box-containing proteins also blocked ERα coactivation by SNURF. However, cotransfection of SNURF with prototypical steroid receptor coactivators 1, 2, and 3 that contain LXXLL box motifs did not enhance E2 responsiveness, whereas TATA-binding protein (TBP) and SNURF cooperatively coactivated ERα-mediated transactivation. The results are consistent with a unique model for cooperative coactivation of ERα that requires ligand binding, repositioning of helix 12, recruitment of TBP, and interaction with SNURF, which binds both ERα and TBP.

Original languageEnglish (US)
Pages (from-to)2485-2497
Number of pages13
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
StatePublished - Jan 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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