BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb
BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb
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DOI：
10.1038/sj.onc.1204048
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发表时间：
2001-01-04
期刊：
影响因子：
8
通讯作者：
Lipsick, JS
中科院分区：
文献类型：
--
作者：
Ladendorff, NE;Wu, S;Lipsick, JS
c-Myb的羧基末端含有一个负调控结构域，该结构域在v-Myb癌蛋白中不存在，但在所有已知的动物Myb蛋白中是保守的。该结构域抑制动物细胞中c-Myb的转录激活，但不抑制芽殖酵母中的转录激活，这表明动物细胞中存在的额外蛋白质而非酵母是该负调控功能所需的。酵母双杂交筛选鉴定出BS 69（一种腺病毒E1 A相关蛋白）与c-Myb的羧基末端区域相互作用，BS 69含有与PHD指、溴结构域和MYND结构域相似的区域，所有这些都在存在于调节转录和/或修饰染色质结构的高分子量复合物中的其他蛋白质中发现。进一步的研究表明，BS 69抑制c-Myb的转录活性，这种抑制是特异性的，它映射到两种蛋白质的羧基末端，并且它是剂量依赖性的。此外，289 R E1 A蛋白还能抑制BS 69介导的c-Myb对转录激活的抑制作用。与EIA抑制Rb/E2 F调节轴类似，我们认为BS 69/Myb调节回路也可能是肿瘤发生过程中的一个破坏靶点。
The carboxyl terminus of c-Myb contains a negative regulatory domain that is absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional protein(s) present in animal cells but not yeast are required for this negative regulatory function. A yeast two-hybrid screen identified BS69, an adenovirus E1A-associated protein, as interacting with the carboxy-terminal region of c-Myb, BS69 contains regions of similarity to the PHD finger, the bromodomain, and the MYND domain, all of which are found in other proteins present in high molecular weight complexes that regulate transcription and/or modify chromatin structure. Further study showed that BS69 inhibited the transcriptional activity of c-Myb, that this inhibition was specific, that it mapped to the carboxyl termini of the two proteins and that it was dose-dependent. A direct interaction between these two proteins was observed in vitro, Furthermore, the 289R E1A protein could inhibit the BS69-mediated decrease in transcriptional activation by c-Myb, By analogy with the inhibition of the Rb/E2F regulatory axis by EIA, we propose that a BS69/Myb regulatory circuit may also be a target of disruption during oncogenesis.