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p53 protein is a suppressor of papillomavirus DNA amplificational replication
D Lepik1, I Ilves, A Kristjuhan
1Department of Microbiology and Virology, Institute of Molecular and Cell Biology, Tartu University and Estonian Biocentre, Tartu EE2400, Estonia.
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.
Insights
The p53 protein inhibits papillomavirus DNA replication by targeting specific domains, without affecting other viral replication cycles or causing cell death. This suggests a crucial role for p53 in managing viral infections.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- The p53 protein is a critical tumor suppressor involved in DNA repair and apoptosis.
- Papillomaviruses rely on host cell machinery for their replication, making them potential targets for cellular regulators.
Purpose of the Study:
- To investigate the effect of the p53 protein on the replication of human and bovine papillomaviruses.
- To identify the specific domains of p53 essential for its antiviral activity.
Main Methods:
- Assessing the impact of p53 on papillomavirus DNA replication in cell cultures.
- Mutational analysis of p53 domains to determine their role in replication suppression.
Main Results:
- p53 effectively blocked the amplificational replication of human and bovine papillomaviruses.
- Specific p53 domains (oligomerization, DNA-binding, RPA-binding, proline-rich) were essential for this inhibitory activity.
- p53 did not inhibit Epstein-Barr virus replication or induce cell cycle arrest or apoptosis.
Conclusions:
- The p53 protein possesses intrinsic activity to suppress papillomavirus amplificational replication.
- This suppression is mediated by specific structural domains of p53 and is independent of cell cycle regulation or apoptosis.
- p53's role in inhibiting viral replication may be significant in virus-cell interactions and the viral life cycle.