%0 Journal Article %A Keblusek, Petra %A Dorsman, Josephine C. %A Teunisse, Amina F. A. S. %A Teunissen, Hans %A van der Eb, Alex J. %A Zantema, Alt %T The adenoviral E1A oncoproteins interfere with the growth-inhibiting effect of the cdk-inhibitor p21(CIP1/WAF1) %D 1999 %J Journal of General Virology, %V 80 %N 2 %P 381-390 %@ 1465-2099 %R https://doi.org/10.1099/0022-1317-80-2-381 %I Microbiology Society, %X The cdk-inhibitor p21(CIP1/WAF1) inhibits the activities of cyclin-dependent kinases and proliferating cell nuclear antigen, thereby repressing cell-cycle progression and DNA replication. Transforming oncogenes, such as E1A of human adenovirus 5 (Ad5), may interfere with such growth-inhibitory proteins. In this study, we show that in various Ad5E1-transformed cells, p21(CIP1/WAF1) is expressed and that, in general, expression is not downregulated. In addition, colony-formation assays show that in Ad5E1-transformed cells highly overexpressed p21(CIP1/WAF1) can still cause growth inhibition. FACS experiments indicate, however, that a G1 arrest induced by moderate overexpression of p21(CIP1/WAF1) can be overcome by E1A. The E1A proteins may interfere with the function of p21(CIP1/WAF1) by binding. Indeed, p21(CIP1/WAF1) binds with its cyclin/cdk-binding N terminus to the transforming N-terminal and CR1 region of the E1A proteins. Together, these results lend support to the model that E1A can interfere directly with p21(CIP1/WAF1) function and thereby stimulates cell growth. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-80-2-381