Chen R H, Fields S, Lipsick J S
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook 11794-5222, USA.
Oncogene. 1995 Nov 2;11(9):1771-9.
The nuclear oncoprotein v-Myb is a transcriptional activator in both animal cells and the budding yeast Saccharomyces cerevisiae. Previous studies have suggested that an acidic domain of approximately 50 amino acids (amino acids 204-254 of v-Myb) is necessary and sufficient for transcriptional activation by v-Myb, c-Myb and GAL4-Myb fusion proteins. However, we find that first, none of the acidic residues within this region is essential for transcriptional activation in either animal cells or yeast. Second, transcriptional activation requires cooperation among multiple domains of v-Myb. In animal cells, transcriptional activation by v-Myb requires a central domain (amino acids 234-295), a C-terminal domain (amino acids 295-356), plus either of two more N-terminal domains (amino acids 163-197 or 198-232); in yeast, it requires the central domain plus either the C-terminal domain or a more N-terminal domain (amino acids 163-233). Third, although various subsets of these domains are sufficient for transcriptional activation by v-Myb, all of the domains must be present for transformation of primary hematopoietic cells. These results demonstrate that transcriptional activation by v-Myb is not sufficient for oncogenic transformation.
核癌蛋白v-Myb在动物细胞和出芽酵母酿酒酵母中都是一种转录激活因子。先前的研究表明，一个约50个氨基酸的酸性结构域（v-Myb的第204 - 254位氨基酸）对于v-Myb、c-Myb和GAL4-Myb融合蛋白的转录激活是必要且充分的。然而，我们发现，首先，该区域内的酸性残基在动物细胞或酵母中对于转录激活都不是必需的。其次，转录激活需要v-Myb的多个结构域协同作用。在动物细胞中，v-Myb的转录激活需要一个中央结构域（第234 - 295位氨基酸）、一个C端结构域（第295 - 356位氨基酸），以及两个N端结构域中的任意一个（第163 - 197位氨基酸或第198 - 232位氨基酸）；在酵母中，它需要中央结构域加上C端结构域或一个更靠N端的结构域（第163 - 233位氨基酸）。第三，虽然这些结构域的不同子集对于v-Myb的转录激活是足够的，但所有结构域都必须存在才能实现原代造血细胞的转化。这些结果表明，v-Myb的转录激活不足以导致致癌转化。
