p53 Protein Is a Suppressor of Papillomavirus DNA Amplificational Replication

Abstract

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

Cell-Specific Modulation of Papovavirus Replication by Tumor Suppressor Protein p53

“…The stability and expression level of the mutant p53 proteins was tested in 10(1) by Western blot analysis. The pattern of expression was the same as in CHO4.15 (20).…”

“…Bovine papillomavirus type 1 (BPV-1) E1 expression vector pCGEag, E2 expression vector pCGE2, and minimal replication origin plasmid pUCAlu have been described previously (4,44). Human p53 deletion mutants were created by PCR and expressed from the pCG vector (20). The mutant protein SR␣⌬N39 expression vector was generated by removing the cytomegalovirus (CMV) promoter from the pCG vector with Ecl136 and EcoRI and replacing it with the SR␣ promoter from the vector pBJ5GS (29) by blunt-end cloning.…”

“…suppressed by the p53 protein in mouse fibroblasts. p53 protein suppresses the papillomavirus origin-dependent replication in hamster and human cells (20). We decided to study the presumed differential effect of the p53 protein on the replication of Py and papillomavirus origins in mouse cells, because previous studies suggested that Py replication is not influenced by this protein (17,23).…”

“…We tested a set of mutant p53 proteins (schematically depicted in Fig. 2A) for their activity to suppress the amplificational replication of the BPV-1 origin in the CHO4.15 cell line (20). In those cells p53 was able to block the replication of the papillomavirus origin.…”

“…In our previous work we demonstrated that p53 could efficiently block the amplificational replication of the papillomavirus origin. This activity of p53 is determined by the RPA binding, proline-rich regulatory, DNA binding, and oligomerization domains of the p53 protein (20). The inhibition of replication seemed to be direct, not making use of the abilities of p53 to block the cell cycle or direct cells to apoptosis.…”