TY - JOUR
T1 - Cooperative coactivation of estrogen receptor α in ZR-75 human breast cancer cells by SNURF and TATA-binding protein
AU - Saville, Bradley
AU - Poukka, Hetti
AU - Wormke, Mark
AU - Jänne, Olli A.
AU - Palvimo, Jorma J.
AU - Stoner, Matthew
AU - Samudio, Ismael
AU - Safe, Stephen
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/1/25
Y1 - 2002/1/25
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M109021200
DO - 10.1074/jbc.M109021200
M3 - Article
C2 - 11696545
AN - SCOPUS:0037169548
SN - 0021-9258
VL - 277
SP - 2485
EP - 2497
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 4
ER -