Firlej Virginie, Bocquet Béatrice, Desbiens Xavier, de Launoit Yvan, Chotteau-Lelièvre Anne
Laboratoire de Biologie du Développement UPRES-EA1033, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
J Biol Chem. 2005 Jan 14;280(2):887-98. doi: 10.1074/jbc.M408017200. Epub 2004 Oct 5.
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.
Ets家族的Pea3转录因子（属于PEA3组）已被证明参与乳腺胚胎发生和肿瘤发生。然而，除了蛋白酶外，其靶基因报道较少。在本报告中，我们鉴定出bax是一个受Pea3上调的基因。我们通过在乳腺细胞系中过表达和沉默Pea3提供了这种调控的证据。Pea3和PEA3组的另一个成员Erm都能够反式激活bax启动子片段。虽然最小的受Pea3调控的bax启动子不包含Ets结合位点，但存在两个功能性的上游刺激因子调控的E盒。我们进一步证明了Pea3和USF-1协同反式激活bax启动子的能力，E盒的突变显著降低了Pea3的反式激活潜能。虽然Pea3不直接与最小的bax启动子结合，但我们提供证据表明USF-1可以与Pea3和DNA形成三元复合物。综上所述，我们的结果表明，Pea3可能通过与USF-1相互作用而不与DNA结合来调控bax转录。
