MYB AND ETS PROTEINS COOPERATE IN TRANSCRIPTIONAL ACTIVATION OF THE MIM-1 PROMOTER
MYB AND ETS PROTEINS COOPERATE IN TRANSCRIPTIONAL ACTIVATION OF THE MIM-1 PROMOTER
复制标题
DOI：
10.1073/pnas.89.4.1291
复制
发表时间：
1992-02-15
影响因子：
11.1
通讯作者：
REDDY, EP
中科院分区：
文献类型：
--
作者：
DUDEK, H;TANTRAVAHI, RV;REDDY, EP
在急性转化禽逆转录病毒E26的产生中，myb和ets基因都被转导，导致产生Gag-Myb-Ets融合蛋白。这种v-myb和v-ets癌基因的共同出现表明两者可能存在功能关系。为了寻找这种关系，我们测试了Myb单独或与共表达的Ets-1或Ets-2的转录激活活性。使用v-Myb诱导型mim-1基因的启动子作为靶标，我们发现全长c-Myb基因产物是较差的转录激活因子，而该蛋白质的致癌（截短）形式是强的反式激活因子。然而，Ets-2与全长或截短形式的Myb的共表达大大增加了反式激活。Ets-1、Fos、Jun或Myc与Myb的共表达不增加mim-1启动子的反式激活。Myb和Ets-2反式激活的能力是合作的，因为Ets-2单独给很少或没有激活。发现细菌合成的Ets-2蛋白特异性结合mim-1启动子，表明它可能是Myb和Ets蛋白的靶点。因此，Myb和Ets蛋白可以在转录激活中合作，并且它们在E26病毒中的共同出现可能反映了这两种癌蛋白之间的功能关系。Myb的截短形式可能减少了对协同因子如Ets-2的需要，这可能构成与致癌激活相关的重要机制。
In the generation of the acutely transforming avian retrovirus E26, both myb and ets genes have been transduced, leading to the production of a Gag-Myb-Ets fusion protein. This co-occurrence of v-myb and v-ets oncogenes suggests that the two might have a functional relationship. To look for such a relationship, we tested the transcriptional activation activity of Myb alone or with coexpressed Ets-1 or Ets-2. Using the promoter of the v-Myb-inducible mim-1 gene as a target, we found that full-length c-Myb gene products were poor activators of transcription, while an oncogenic (truncated) form of this protein was a strong trans-activator. However, coexpression of Ets-2 with full-length or truncated forms of Myb greatly increased trans-activation. Coexpression of Ets-1, Fos, Jun, or Myc with Myb did not increase trans-activation of the mim-1 promoter. The ability of Myb and Ets-2 to transactivate was cooperative, since Ets-2 alone gave little or no activation. Bacterially synthesized Ets-2 protein was found to bind specifically to the mim-1 promoter, suggesting that it may be a target for both Myb and Ets proteins. Thus, Myb and Ets proteins can cooperate in transcriptional activation, and their co-occurrence in the E26 virus may reflect a functional relationship between these two oncoproteins. Truncated forms of Myb may have a reduced need for cooperating factors such as Ets-2, and this might constitute an important mechanism associated with oncogenic activation.