Modulation of AP‐1/ATF transcription factor activity by the adenovirus‐e1a oncogene products

Abstract

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.