Carrère S, Verger A, Flourens A, Stehelin D, Duterque-Coquillaud M
CNRS UMR 319, Institut de Biologie de Lille, France.
Oncogene. 1998 Jun 25;16(25):3261-8. doi: 10.1038/sj.onc.1201868.
The ets genes family encodes a group of proteins which function as transcription factors under physiological conditions. We report here that the Erg proteins, members of the Ets family, form homo and heterodimeric complexes in vitro. We demonstrate that the Ergp55 protein isoform forms dimers with itself and with the two other isoforms, Ergp49 and Ergp38. Using a set of Erg protein deletion mutants, we define two distinct domains independently involved in dimerization. The first one is located in the amino-terminal part of the protein containing the pointed domain (PNT), conserved in a subset of Ets proteins. The second one resides within the ETS domain, the DNA-binding domain. We also show that the Erg protein central region behaves as an inhibitory domain of dimerization and its removal enhances the Ergp55 transactivation properties. Furthermore, Ergp55 forms heterodimers with some other Ets proteins. Among the latter, we show that Fli-1, Ets-2, Er81 and Pu-1 physically interact with Erg. Finally, we show that the formation of the previously described ternary complex Ergp55/Fos/jun is mediated by ETS domain and Jun protein, while the ternary complex Ergp49/Fos/Jun is mediated by Fos protein.
ets基因家族编码一组在生理条件下起转录因子作用的蛋白质。我们在此报告，Ets家族成员Erg蛋白在体外形成同二聚体和异二聚体复合物。我们证明，Ergp55蛋白异构体可与自身以及另外两种异构体Ergp49和Ergp38形成二聚体。通过一组Erg蛋白缺失突变体，我们确定了两个独立参与二聚化的不同结构域。第一个位于蛋白质的氨基末端部分，包含在一部分Ets蛋白中保守的尖结构域（PNT）。第二个位于ETS结构域内，即DNA结合结构域。我们还表明，Erg蛋白的中央区域表现为二聚化的抑制结构域，去除该区域可增强Ergp55的反式激活特性。此外，Ergp55与其他一些Ets蛋白形成异二聚体。在后者中，我们表明Fli-1、Ets-2、Er81和Pu-1与Erg发生物理相互作用。最后，我们表明，先前描述的三元复合物Ergp55/Fos/jun的形成由ETS结构域和Jun蛋白介导，而三元复合物Ergp49/Fos/Jun由Fos蛋白介导。
