RT Journal Article SR Electronic(1) A1 Keblusek, Petra A1 Dorsman, Josephine C. A1 Teunisse, Amina F. A. S. A1 Teunissen, Hans A1 van der Eb, Alex J. A1 Zantema, AltYR 1999 T1 The adenoviral E1A oncoproteins interfere with the growth-inhibiting effect of the cdk-inhibitor p21(CIP1/WAF1) JF Journal of General Virology, VO 80 IS 2 SP 381 OP 390 DO https://doi.org/10.1099/0022-1317-80-2-381 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-80-2-381