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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein
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Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein

机译：转移相关蛋白1（MTA1）是c-MYC癌蛋白的重要下游效应子

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摘要

The c-myc oncogene is among the most commonly overexpressed genes in human cancer. c-myc encodes a basic helix-loop- helix/ leucine zipper (bHLH/LZ) transcription factor (c-MYC) that activates a cascade of downstream targets that ultimately mediate cellular transformation. Although a large number of genes are regulated by c-MYC, only a few have been functionally linked to c-MYC-mediated transformation. By expression profiling, the metastasis-associated protein 1 (MTA1) gene was identified here as a target of the c-MYC oncoprotein in primary human cells, a result confirmed in human cancer cells. MTA1 itself has been previously implicated in cellular transformation, in part through its ability to regulate the epithelial-to-mesenchymal transition and metastasis. MTA1 is a component of the Mi-2ucleosome remodeling and deacetylating (NURD) complex that contains both histone deacetylase and nucleosome remodeling activity. The data reported here demonstrate that endogenous c-MYC binds to the genomic MTA1 locus and recruits transcriptional coactivators. Most importantly, short hairpin RNA (shRNA)-mediated knockdown of MTA1 blocks the ability of c-MYC to transform mammalian cells. These data implicate MTA1 and the Mi-2/NURD complex as one of the first downstream targets of c-MYC function that are essential for the transformation potential of c-MYC.
机译：c-myc癌基因是人类癌症中最常见的过度表达基因之一。 c-myc编码基本的螺旋-环-螺旋/亮氨酸拉链（bHLH / LZ）转录因子（c-MYC），该转录因子激活一系列下游靶标，最终介导细胞转化。尽管大量基因受c-MYC调控，但只有少数基因在功能上与c-MYC介导的转化有关。通过表达谱分析，此处将转移相关蛋白1（MTA1）基因鉴定为原代人细胞中c-MYC癌蛋白的靶标，这一结果在人癌细胞中得到证实。 MTA1本身以前就参与了细胞转化，部分原因是它具有调节上皮到间充质转化和转移的能力。 MTA1是包含组蛋白脱乙酰基酶和核小体重塑活性的Mi-2 /核小体重塑和去乙酰化（NURD）复合物的组成部分。此处报道的数据证明内源性c-MYC与基因组MTA1基因座结合并募集转录共激活因子。最重要的是，短发夹RNA（shRNA）介导的MTA1敲低可阻断c-MYC转化哺乳动物细胞的能力。这些数据表明，MTA1和Mi-2 / NURD复合体是c-MYC功能的第一个下游靶标之一，对c-MYC的转化潜力至关重要。

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