Transforming region of 243R E1A contains two overlapping but distinct transactivation domains.-猫眼课题宝

243R E1A 的转化区包含两个重叠但不同的反式激活结构域。

DOI：

10.1089/dna.1997.16.1321

发表时间：

1997

期刊：

DNA and cell biology.

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Sang,N;Claudio,PP;Fu,Y;Horikoshi,N;Graeven,U;Weinmann,R;Giordano,A

Conserved regions 1 and 2 as well as the amino terminus of E1A are required for the transforming activity of the E1A oncoprotein. We show here that the amino terminus of 243R E1A has transactivation activity when brought to a promoter in yeast. Recruitment to a specific promoter is essential. Mutagenesis studies correlated the transactivation function with the extreme amino terminus and the conserved region 1 of E1A. Cotransfection assays in rodent cells confirmed that two overlapping but distinguishable domains, amino acids 1-65 and 37-80, can transactivate independently when targeted to a promoter. We also observed that when recruited to the proliferating cell nuclear antigen (PCNA) promoter, the amino-terminal region was sufficient to transactivate thePCNApromoter. On the other hand, deletion of the amino terminus of E1A resulted in failure to inducePCNAexpression. Fusion of VP16 with the amino-terminal-deleted E1A mutant was able to restore the ability to induce thePCNApromoter. We further show that the amino-terminal region also is required for 243R E1A to repress the transactivation mediated by a universal transactivator DBD.VP16 and DBD.E1A. This repression could be specifically relieved by overexpression of TBP but not TFIIB. In addition, we show that the amino terminus of E1A is involved inin vitrointeraction with the TATA binding protein (TBP). Thus the amino-terminal transforming region of E1A may regulate cellular gene expression in species that are distant in evolution via a common mechanism, functionally targeting TBP.