期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：5
页码：1782-1786
DOI：10.1073/pnas.87.5.1782
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Expression studies of the early EIIa transcription unit (EIIaE) of the adenovirus EIa-deletion mutant dl312 in murine embryonal carcinoma stem cells suggested that these cells contain an activity that substitutes for the viral EIa. To further characterize this cellular EIa-like activity, we analyzed expression of the EIIaE promoter as well as the binding activity of the cognate E2F transcription factor after infection of F9 embryonal carcinoma cells and their differentiated derivatives with wild-type adenovirus, EIa (dl312), or EIV (dl808) deletion mutants. We show that, in contrast to the viral EIa proteins that transactivate the EIIaE promoter in F9 cells only after differentiation, the viral EIV products activate the EIIaE promoter most efficiently in undifferentiated F9 cells. We also show that the EIV products induce a specific modification of the E2F transcription factor leading to its cooperative binding to the EIIaE promoter. Although the EIa-dependent transactivation of EIIaE in differentiated cells is also in part mediated by E2F, it does not by itself correlate with the simultaneous binding of two E2F molecules. In these cells E2F dimer binding only occurs as a secondary effect of EIa that also stimulates EIV expression. Our results suggest that EIa and EIV act through separate pathways, inversely regulated during cell differentiation, with the so-called "EIa-like" activity contributing to this modulation.
