The carboxyterminus of human c-myb protein stimulates activated transcription in trans
The carboxyterminus of human c-myb protein stimulates activated transcription in trans
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人c-myb蛋白的羧基末端刺激反式转录激活
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
K. Moelling
中科院分区：
文献类型：
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作者：
G. Vorbrueggen;F. Kalkbrenner;S. Guehmann;K. Moelling
C-myb基因编码一个转录因子，由DNA结合区、反式激活区和位于其羧基末端的调节区组成。后者在转化病毒蛋白v-Myb中缺失。在这里，我们发现c-Myb的C末端的缺失增加了c-Myb的转录反式激活活性，将其定义为顺式作用的负调节域。在体内竞争试验中，C末端的共转染会刺激各种v-和c-Myb表达结构在反式中的转录活性。由于c-Myb和GAL4-c-Myb嵌合体可以在反式刺激下被刺激，所以这种作用是剂量依赖的，与DNA结合域的种类无关。其他转录因子，如GAL4-VP16、GAL4、c-jun或C/EBPβ也被共转染的C-末端所激活。相反，人的B-Myb在反式中不受c-Myb C末端的刺激。这些数据表明，c-Myb的C末端可能与细胞抑制物相互作用，后者是介导激活转录的蛋白质复合体的一部分，并可能通过隔离这种抑制物来刺激反式转录。C-Myb与假定的抑制物结合可以解释c-Myb与B-Myb和v-Myb在转录调控方面的差异。
The cellular c-myb gene encodes a transcription factor composed of a DNA-binding domain, a transactivating domain and a regulatory domain located at its carboxy (C-) terminus. The latter one is deleted in the transforming viral protein v-Myb. Here we show that deletion of the C-terminus of c-Myb increases the transcriptional transactivation activity of c-Myb defining it as cis-acting negative regulatory domain. Cotransfection of the C-terminus in an in vivo competition assay causes stimulation of the transcriptional activity of various v- and c-Myb expression constructs in trans. The effect is dose-dependent and independent of the kind of DNA-binding domain, since c-Myb as well as GAL4-c-Myb chimaeras can be stimulated in trans. Other transcription factors, such as GAL4-VP16, GAL4, c-Jun or C/EBP beta are also stimulated by the cotransfected C-terminus. In contrast, human B-Myb is not stimulated by the c-Myb C-terminus in trans. The data suggest that the C-terminus of c-Myb may interact with a cellular inhibitor which is part of the protein complex mediating activated transcription and may stimulate in trans by sequestering away such an inhibitor. Binding of c-Myb to a putative inhibitor would explain differences between c-Myb in comparison to B- and v-Myb in transcriptional regulation.