Kraut N, Frampton J, Graf T
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Oncogene. 1995 Mar 16;10(6):1027-36.
The Myb-Ets oncoprotein encoded by the E26 avian leukaemia virus represents a fusion of two transcription factors which cooperate in transforming multipotent haematopoietic progenitors (MEPs) in vitro and in vivo. Previous studies with a temperature sensitive mutant in ets (ts1.1 E26) have suggested that the Ets part of the Myb-Ets fusion protein blocks multilineage differentiation of transformed MEPs, by regulating specific target genes. Using this system in a differential screening approach we have now identified a new gene, called rem-1, as a target for the E26 virus. Following shift of ts1.1 mutant transformed cells to the nonpermissive temperature a decreased expression of rem-1 was observed which increased upon downshift. The finding that this reexpression did not require new protein synthesis suggests that the Ets component of the fusion protein directly regulates rem-1 transcription. Rem-1 is related to a family of EF-hand-containing calcium-binding proteins that are predominantly expressed in the brain and in retinal cells. This family includes recoverin and visinin, proteins that have been implicated in regulating photoreception. Rem-1 is likewise expressed in these tissues but in addition in haematopoietic cells and in the gut. Enforced expression of rem-1 in ts1.1-transformed MEP cells, using a retroviral vector, showed that this gene is not sufficient to block their differentiation, but that it may provide them with a growth advantage.
由E26禽白血病病毒编码的Myb-Ets癌蛋白代表了两种转录因子的融合,这两种转录因子在体外和体内协同作用,可转化多能造血祖细胞(MEP)。先前对ets温度敏感突变体(ts1.1 E26)的研究表明,Myb-Ets融合蛋白的Ets部分通过调节特定靶基因来阻断转化的MEP的多系分化。利用该系统进行差异筛选,我们现已鉴定出一个名为rem-1的新基因,它是E26病毒的一个靶标。将ts1.1突变体转化细胞转移至非允许温度后,观察到rem-1表达降低,而温度降低时其表达增加。重新表达不需要新的蛋白质合成这一发现表明,融合蛋白的Ets成分直接调节rem-1转录。Rem-1与一类含EF手型钙结合蛋白家族相关,这些蛋白主要在大脑和视网膜细胞中表达。该家族包括恢复蛋白和视宁蛋白,这些蛋白与调节光感受有关。Rem-1同样在这些组织中表达,但此外还在造血细胞和肠道中表达。使用逆转录病毒载体在ts1.1转化的MEP细胞中强制表达rem-1,结果表明该基因不足以阻断它们的分化,但可能为它们提供生长优势。