Pea3 transcription factor cooperates with USF-1 in regulation of the murine bax transcription without binding to an Ets-binding site.
The Pea3 transcription factor (which belongs to the PEA3 group) from the Ets family has been shown to be involved in mammary embryogenesis and oncogenesis. However, except for proteinases, only few of its target genes have been reported. In the present report, we identified bax as a Pea3 up-regulated gene. We provide evidence of this regulation by using Pea3 overexpression and Pea3 silencing in a mammary cell line. Both Pea3 and Erm, another member of the PEA3 group, are able to transactivate bax promoter fragments. Although the minimal Pea3-regulated bax promoter does not contain an Ets-binding site, two functional upstream stimulatory factor-regulated E boxes are present. We further demonstrate the ability of Pea3 and USF-1 to cooperate for the transactivation of the bax promoter, mutation of the E boxes dramatically reducing the Pea3 transactivation potential. Although Pea3 did not directly bind to the minimal bax promoter, we provide evidence that USF-1 could form a ternary complex with Pea3 and DNA. Taken together, our results suggest that Pea3 may regulate bax transcription via the interaction with USF-1 but without binding to DNA.
Laboratoire de Biologie du Développement UPRES-EA1033, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Virginie
V
Firlej
Béatrice
B
Bocquet
Xavier
X
Desbiens
Yvan
Y
de Launoit
Anne
A
Chotteau-Lelièvre
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D011770:Pyruvate Kinase / Q000235:genetics; D020218:Response Elements / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D051720:Upstream Stimulatory Factors; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050783:Proto-Oncogene Proteins c-ets; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D051028:bcl-2-Associated X Protein; C065788:transcription factor PEA3; D011770:Pyruvate Kinase