B-myb, a repressed trans-activating protein
B-myb, a repressed trans-activating protein
复制标题
DOI：
10.1007/s001090050170
复制
发表时间：
1997-11-01
影响因子：
4.7
通讯作者：
Leutz, A
中科院分区：
文献类型：
--
作者：
Ansieau, S;KowenzLeutz, E;Leutz, A
B-Myb属于一个具有独特DNA结合结构域的转录因子家族。B-Myb在细胞周期调控中起重要作用。其表达被人乳头瘤病毒HPV 16 E7癌蛋白上调。过表达B-Myb可以绕过p53介导的细胞周期阻滞。myb基因家族的创始成员c-Myb和A-Myb分别参与造血和神经发生，并且都是基因转录的激活剂。然而，B-Myb是反式激活因子还是阻遏因子仍然是一个讨论的问题。我们回顾了B-Myb在酵母中的反式激活潜力，利用这一事实，诱导基因激活是一个进化保守的过程。通过突变分析，我们在B-Myb中定位了一个保守的激活结构域。在脊椎动物细胞中，B-Myb的反式激活潜力被蛋白质的C-末端部分隐藏。我们发现，细胞周期调节因子细胞周期蛋白A和细胞周期蛋白E激活B-Myb消除其羧基末端介导的抑制。我们的数据表明，在脊椎动物中，B-Myb的反式激活功能在细胞周期中受到调节，并将Myb功能与细胞周期进程联系起来。
B-Myb belongs to a family of related transcription factors which share a unique DNA binding domain. B-Myb plays an important role in regulation of the cell cycle. Its expression is upregulated by the human papilloma virus HPV16 E7 oncoprotein. Overexpression of B-Myb can bypass p53-mediated cell cycle arrest. The founding member of the myb gene family, c-Myb, and A-Myb are involved in hematopoiesis and neurogenesis, respectively, and are both activators of gene transcription. Whether B-Myb is a transactivator or a repressor, however, has remained a matter of discussion. We reviewed the transactivation potential of B-Myb in yeast, taking advantage of the fact that inducible gene activation is an evolutionarily conserved process. By mutational analysis we localized a conserved activation domain in B-Myb. In vertebrate cells the transactivation potential of B-Myb is concealed by the C-terminal part of the protein. We show that the cell cycle regulators cyclin A and cyclin E activate B-Myb by eradicating the inhibition mediated by its carboxy-terminus. Our data suggest that in vertebrates the trans-activating function of B-Myb is regulated during the cell cycle and link Myb functions to cell cycle progression.