p53 protein was able to block human and bovine papillomavirus DNA ampl
ificational replication while not interfering with Epstein-Barr virus
oriP once-per-cell cycle replication. Oligomerization, intact DNA-bind
ing, replication protein A-binding, and proline-rich domains of the p5
3 protein were essential for efficient inhibition, while the N-termina
l transcriptional activation and C-terminal regulatory domains were di
spensable for the suppressor activity of the p53 protein. The inhibiti
on of replication was caused neither by the downregulation of expressi
on of the E1 and E2 proteins nor by cell cycle block or apoptosis. Our
data suggest that the intrinsic activity of p53 to suppress amplifica
tional replication of the papillomavirus origin may have an important
role in the virus life cycle and in virus-cell interactions.