MODULATION OF AP-1 ATF TRANSCRIPTION FACTOR ACTIVITY BY THE ADENOVIRUS-E1A ONCOGENE PRODUCTS/

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 EIA pro teins redirect the cell's metabolism, which enables them to induce onc ogenic transformation in rodent cells. The E1A proteins modulate trans cription by interacting both with gene-specific and general cellular t ranscription factors. Various members of the AP-1 and ATF/CREB familie s of transcription factors are targets for E1A-dependent regulation, i ncluding cJun, the protein product of the c-jun proto-oncogene. The E1 A proteins modulate cJun-dependent transcription both positively and n egatively, and affect the activity as well as the expression levels of cJun. By increasing the phosphorylation status of cJun, E1A can stimu late transcription regulated by cJun/ATF2 heterodimers. In contrast, E 1A 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 transcriptiona l coactivator p300. Since the ability of E1A to alter cJun-dependent t ranscription correlates with its transforming capacity, interference w ith cJun-dependent transcription may be an essential step in E1A-induc ed transformation.