Schuck, S., Ruse, C., Stenlund, A. (May 2013) CK2 phosphorylation inactivates DNA binding by the papillomavirus E1 and E2 proteins. Journal of Virology, 87 (13). pp. 7668-7679. ISSN 0022-538X
Abstract
Papillomaviruses have complex life cycles that are only superficially understood. Although it is well established that the viral E1 and E2 proteins play key roles in controlling viral transcription and DNA replication, how these factors are regulated is not well understood. Here we demonstrate that phosphorylation by the protein kinase CK2 controls the biochemical activities of the bovine papillomavirus E1 and E2 proteins by modifying their DNA binding activity. Phosphorylation at multiple sites in the N-terminal domain in E1 results in the loss of sequence-specific DNA binding activity - a feature that is also conserved in HPV E1 proteins. The BPV E2 protein, when phosphorylated by CK2 on two specific sites in the hinge, also loses its site-specific DNA binding activity. Mutation of these sites in E2 result in greatly increased levels of latent viral DNA replication, indicating that CK2 phosphorylation of E2 is a negative regulator of viral DNA replication during latent viral replication. In contrast, mutation of the N-terminal phosphorylation sites in E1 has no effect on latent viral DNA replication. We propose that the phosphorylation of the N-terminus of E1 plays a role only in vegetative viral DNA replication, and consistent with such a role, Caspase 3 cleavage of E1, which has been shown to be necessary for vegetative viral DNA replication, restores the DNA binding activity to phosphorylated E1.
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