Miller M E, Cairns B R, Levinson R S, Yamamoto K R, Engel D A, Smith M M
Department of Microbiology, School of Medicine, University of Virginia Charlottesville 22908, USA.
Mol Cell Biol. 1996 Oct;16(10):5737-43. doi: 10.1128/MCB.16.10.5737.
Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.
腺病毒E1A243癌蛋白在酿酒酵母中的表达产生了一种生长缓慢的表型，细胞在细胞周期的G1期积累。这种效应归因于E1A243的N端和CR1结构域，在啮齿动物细胞中，它们参与触发细胞转化以及与细胞转录共激活因子p300结合。进行了一项遗传筛选，以鉴定酿酒酵母中E1A243功能所需的基因。该筛选鉴定出SNF12，一个编码SWI/SNF转录调节复合物73-kDa亚基的基因。编码SWI/SNF复合物已知成员的基因突变也导致E1A功能丧失，这表明SWI/SNF复合物是E1A243的一个靶点。此外，E1A在野生型细胞中的表达特异性地阻断了INO1和SUC2基因的转录激活，它们的激活途径不同，但对SWI/SNF复合物有共同需求。这些数据证明了E1A与SWI/SNF复合物之间存在特定的功能相互作用，并表明在啮齿动物和人类细胞中发生了类似的相互作用。
