Liu F, Lei W, O'Rourke J P, Ness S A
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001, USA.
Oncogene. 2006 Feb 2;25(5):795-805. doi: 10.1038/sj.onc.1209105.
The v-Myb oncoprotein encoded by Avian Myeloblastosis Virus is highly oncogenic, induces leukemias in chickens and mice and transforms immature hematopoietic cells in vitro. The v-Myb protein is a mutated and truncated version of c-Myb, a DNA-binding transcription factor expressed in many cell types that is essential for normal hematopoiesis. Previous studies suggested that two types of differences, DNA binding domain mutations and the deletion of a C-terminal negative regulatory domain were important for increasing the transforming activity of v-Myb. Here, we combined structure-function studies of the v-Myb and c-Myb proteins with unbiased microarray-based transcription assays to compare the transcriptional specificities of the two proteins. In human cells, the v-Myb and c-Myb proteins displayed strikingly different activities and regulated overlapping, but largely distinct sets of target genes. Each type of mutation that distinguished v-Myb from c-Myb, including the N- and C-terminal deletions, DNA binding domain changes and mutations in the transcriptional activation domain, affected different sets of target genes and contributed to the different activities of c-Myb and v-Myb. The results suggest that v-Myb is not just a de-repressed version of c-Myb. Instead, it is a distinct transcriptional regulator with a unique set of activities.
禽成髓细胞瘤病毒编码的v-Myb癌蛋白具有高度致癌性，可在鸡和小鼠中诱发白血病，并在体外转化未成熟造血细胞。v-Myb蛋白是c-Myb的突变和截短版本，c-Myb是一种在多种细胞类型中表达的DNA结合转录因子，对正常造血至关重要。先前的研究表明，DNA结合结构域突变和C端负调控结构域缺失这两种差异对于提高v-Myb的转化活性很重要。在这里，我们将v-Myb和c-Myb蛋白的结构-功能研究与基于微阵列的无偏转录分析相结合，以比较这两种蛋白的转录特异性。在人类细胞中，v-Myb和c-Myb蛋白表现出截然不同的活性，并调控重叠但在很大程度上不同的靶基因集。区分v-Myb与c-Myb的每种突变类型，包括N端和C端缺失、DNA结合结构域变化以及转录激活结构域中的突变，都会影响不同的靶基因集，并导致c-Myb和v-Myb具有不同的活性。结果表明，v-Myb不仅仅是c-Myb的去抑制版本。相反，它是一种具有独特活性集的独特转录调节因子。
