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首页> 外文期刊>Journal of cellular biochemistry. >E1A physically interacts with RUNX3 and inhibits its transactivation activity.
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E1A physically interacts with RUNX3 and inhibits its transactivation activity.

机译：E1A与RUNX3发生物理相互作用并抑制其反式激活活性。

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The adenoviral gene, termed early region 1A (E1A), is crucial for transformation and has been used very effectively as a tool to determine the molecular mechanisms that underlie the basis of cellular transformation. pRb, p107, p130, p300/CBP, p400, TRRAP, and CtBP were identified to be E1A-binding proteins and their roles in cellular transformation have been established. Although the major function of E1A is considered to be the regulation of gene expression that is critical for differentiation and cell cycle exit, one of the most significant questions relating to E1A transformation is how E1A mediates this regulation. RUNX3 is a transcription factor that was first described as a gastric cancer tumor suppressor but is now known to be involved in many different cancers. Exogenous expression of RUNX3 strongly inhibits the growth of cells. Here, we show that the adenovirus oncoprotein E1A interacts with RUNX3 in vitro and in vivo. RUNX3 interacts with the N-terminus (amino acids 2-29) of E1A, which is known to interact with p300/CBP, p400, and TRRAP. E1A interacts directly with the Runt domain of RUNX3 but does not interfere with CBFbeta-RUNX3 interactions. In addition, E1A inhibits the transactivation activity of RUNX3 on the p21(WAF1/CIP1) promoter. Consistent with these observations, the growth inhibition induced by RUNX3 is reduced by E1A. These results demonstrate that E1A specifically binds to RUNX3 and inactivates its transactivation activity. We propose that one of the mechanisms for the oncogenic activity of E1A is the inhibition of RUNX3, similar to that of RB and p300/CBP.
机译：腺病毒基因，称为早期区域1A（E1A），对于转化至关重要，已非常有效地用作确定细胞转化基础分子机制的工具。已确定pRb，p107，p130，p300 / CBP，p400，TRRAP和CtBP是E1A结合蛋白，并且已经确定了它们在细胞转化中的作用。尽管E1A的主要功能被认为是对分化和细胞周期退出至关重要的基因表达调控，但与E1A转化有关的最重要问题之一是E1A如何介导这种调控。 RUNX3是一种转录因子，最初被描述为胃癌肿瘤抑制因子，但现在已知与许多不同的癌症有关。 RUNX3的外源表达强烈抑制细胞的生长。在这里，我们显示腺病毒癌蛋白E1A在体外和体内与RUNX3相互作用。 RUNX3与E1A的N末端（氨基酸2-29）相互作用，已知它与p300 / CBP，p400和TRRAP相互作用。 E1A直接与RUNX3的Runt域交互，但不干扰CBFbeta-RUNX3交互。此外，E1A抑制RUNX3在p21（WAF1 / CIP1）启动子上的反式激活活性。与这些观察结果一致，E1A降低了由RUNX3诱导的生长抑制。这些结果表明，E1A与RUNX3特异性结合并使其反式激活活性失活。我们建议，E1A致癌活性的机制之一是对RUNX3的抑制，类似于RB和p300 / CBP。

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