Cooperative Coactivation of Estrogen Receptor α in ZR-75 Human Breast Cancer Cells by SNURF and TATA-binding Protein* Academic Article uri icon

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 alpha (ERalpha) (4-fold)- and HE19 (ERalpha 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. ERalpha interacted with multiple regions of SNURF; SNURF interactions with ERalpha were dependent on AF2, and D538N, E542Q, and D545N mutations in helix 12 abrogated both SNURF-ERalpha binding and coactivation. Moreover, peptide fusion proteins that inhibit interactions between helix 12 of ERalpha with LXXLL box-containing proteins also blocked ERalpha 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 ERalpha-mediated transactivation. The results are consistent with a unique model for cooperative coactivation of ERalpha that requires ligand binding, repositioning of helix 12, recruitment of TBP, and interaction with SNURF, which binds both ERalpha and TBP.

altmetric score

  • 9

author list (cited authors)

  • Saville, B., Poukka, H., Wormke, M., Jänne, O. A., Palvimo, J. J., Stoner, M., Samudio, I., & Safe, S.

citation count

  • 36

complete list of authors

  • Saville, Bradley||Poukka, Hetti||Wormke, Mark||Janne, Olli A||Palvimo, Jorma J||Stoner, Matthew||Samudio, Ismael||Safe, Stephen

publication date

  • January 2002