Wong H K, Ziff E B
Howard Hughes Medical Institute, Department of Biochemistry, New York University Medical Center, New York 10016.
J Virol. 1994 Aug;68(8):4910-20. doi: 10.1128/JVI.68.8.4910-4920.1994.
The amino-terminal region of the adenovirus type 5 E1a protein including conserved regions (CRs) 1 and 2 binds the 105-kDa retinoblastoma protein and a second, 300-kDa, cellular protein. We show that mutant viruses with deletions of CR1 which release the binding of either p105 or p300 still activate early promoters and infect cells productively. However, mutations which disrupt binding of both proteins disrupt early promoter activity and block the viral life cycle. Ela CR3, which has an established role in early promoter activation, can act in trans to the amino-terminal functions. This suggests that the amino terminus provides distinct, redundant functions related to p300 and Rb binding that synergize with CR3 to transactivate early genes.
腺病毒5型E1a蛋白的氨基末端区域，包括保守区（CRs）1和2，可与105 kDa的视网膜母细胞瘤蛋白以及另一种300 kDa的细胞蛋白结合。我们发现，缺失CR1从而解除与p105或p300结合的突变病毒仍能激活早期启动子并有效感染细胞。然而，破坏这两种蛋白结合的突变会破坏早期启动子活性并阻断病毒生命周期。在早期启动子激活中已确定起作用的E1a CR3，可以反式作用于氨基末端功能。这表明氨基末端提供了与p300和Rb结合相关的独特冗余功能，这些功能与CR3协同作用以反式激活早期基因。
