Chinnadurai G
Institute for Molecular Virology, Saint Louis University School of Medicine, 3681 Park Ave., St. Louis, MO 63110, USA.
Curr Top Microbiol Immunol. 2004;273:139-61. doi: 10.1007/978-3-662-05599-1_5.
The E1A oncogene of human adenoviruses cooperates with other viral and cellular oncogenes in oncogenic transformation of primary and established cells. The N-terminal half of E1A proteins that form specific protein complexes with pRb family and p300/CBP transcriptional regulators is essential for the transforming activities of E1A. Although the C-terminal half of E1A is dispensable for the transforming activities, it negatively modulates the oncogenic activities of the N-terminal region. Mutants of E1A lacking the C-terminal half or a short C-terminal region exhibit a hyper-transforming phenotype in cooperative transformation assays with the activated ras oncogene. The E1A C-terminal region implicated in the oncogenesis-restraining activity interacts with a 48-kDa cellular phosphoprotein, CtBP, that functions as a transcriptional corepressor. It appears that the C-terminal region of E1A may suppress E1A-mediated oncogenic transformation by a dual mechanism of relieving repression cellular genes by CtBP, and also by antagonizing the oncogenic activities of the N-terminal half of E1A.
人类腺病毒的E1A癌基因在原代细胞和已建系细胞的致癌转化过程中，可与其他病毒和细胞癌基因协同作用。E1A蛋白的N端一半可与pRb家族及p300/CBP转录调节因子形成特定的蛋白复合物，这对于E1A的转化活性至关重要。虽然E1A的C端一半对于转化活性并非必需，但它会对N端区域的致癌活性产生负向调节作用。在与激活的ras癌基因进行的协同转化试验中，缺失C端一半或短C端区域的E1A突变体表现出超转化表型。参与致癌抑制活性的E1A C端区域与一种48 kDa的细胞磷蛋白CtBP相互作用，CtBP作为转录共抑制因子发挥作用。看来，E1A的C端区域可能通过双重机制抑制E1A介导的致癌转化，一方面通过解除CtBP对细胞基因的抑制作用，另一方面通过拮抗E1A N端一半的致癌活性。
