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人类c-myb蛋白的羧基末端可反式刺激激活转录。

The carboxyterminus of human c-myb protein stimulates activated transcription in trans.

作者信息

Vorbrueggen G, Kalkbrenner F, Guehmann S, Moelling K

机构信息

Max-Planck-Institut für Molekulare Genetik, Abteilung Schuster, Berlin, Germany.

出版信息

Nucleic Acids Res. 1994 Jul 11;22(13):2466-75. doi: 10.1093/nar/22.13.2466.

Abstract

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.

摘要

细胞c-myb基因编码一种转录因子,该转录因子由一个DNA结合结构域、一个反式激活结构域和一个位于其羧基(C-)末端的调节结构域组成。后者在转化病毒蛋白v-Myb中缺失。在此我们表明,c-Myb 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负调节结构域。在体内竞争试验中共转染C末端会导致各种v-Myb和c-Myb表达构建体的转录活性在反式作用中受到刺激。这种效应是剂量依赖性的,且与DNA结合结构域的类型无关,因为c-Myb以及GAL4-c-Myb嵌合体在反式作用中均可受到刺激。其他转录因子,如GAL4-VP16、GAL4、c-Jun或C/EBPβ也会受到共转染的C末端的刺激。相比之下,人B-Myb在反式作用中不会受到c-Myb C末端的刺激。这些数据表明,c-Myb的C末端可能与一种细胞抑制剂相互作用,该抑制剂是介导激活转录的蛋白质复合物的一部分,并且可能通过隔离这种抑制剂在反式作用中发挥刺激作用。c-Myb与一种假定抑制剂的结合可以解释c-Myb在转录调控方面与B-Myb和v-Myb相比的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b0b/308197/32fb4a99dc35/nar00037-0043-a.jpg

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