Hagmeyer B M, Angel P, van Dam H
Laboratory for Molecular Carcinogenesis, University of Leiden, The Netherlands.
Bioessays. 1995 Jul;17(7):621-9. doi: 10.1002/bies.950170708.
The proteins encoded by early region 1 A (E1A) of human adenoviruses (Ad) modulate the expression of both adenovirus genes and various host cell genes. With these transcription-regulating properties the E1A proteins redirect the cell's metabolism, which enables them to induce oncogenic transformation in rodent cells. The E1A proteins modulate transcription by interacting both with gene-specific and general cellular transcription factors. Various members of the AP-1 and ATF/CREB families of transcription factors are targets for E1A-dependent regulation, including cJun, the protein product of the c-jun proto-oncogene. The E1A proteins modulate cJun-dependent transcription both positively and negatively, and affect the activity as well as the expression levels of cJun. By increasing the phosphorylation status of cJun, E1A can stimulate transcription regulated by cJun/ATF2 heterodimers. In contrast, E1A inhibits the expression of various metalloproteases by interfering with the DNA-binding capacity of cJun/cJun and cJun/cFos dimers, which might involve the association of E1A with the putative transcriptional coactivator p300. Since the ability of E1A to alter cJun-dependent transcription correlates with its transforming capacity, interference with cJun-dependent transcription may be an essential step in E1A-induced transformation.
人类腺病毒（Ad）早期区域1A（E1A）编码的蛋白质可调节腺病毒基因和各种宿主细胞基因的表达。凭借这些转录调节特性，E1A蛋白可改变细胞的新陈代谢，使其能够在啮齿动物细胞中诱导致癌转化。E1A蛋白通过与基因特异性和一般细胞转录因子相互作用来调节转录。转录因子AP-1和ATF/CREB家族的各种成员是E1A依赖性调节的靶标，包括cJun，即c-jun原癌基因的蛋白质产物。E1A蛋白对cJun依赖性转录具有正向和负向调节作用，并影响cJun的活性以及表达水平。通过提高cJun的磷酸化状态，E1A可以刺激由cJun/ATF2异二聚体调节的转录。相反，E1A通过干扰cJun/cJun和cJun/cFos二聚体的DNA结合能力来抑制各种金属蛋白酶的表达，这可能涉及E1A与假定的转录共激活因子p300的结合。由于E1A改变cJun依赖性转录的能力与其转化能力相关，因此干扰cJun依赖性转录可能是E1A诱导转化的关键步骤。
