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CK2 phosphorylation inactivates DNA binding by the papillomavirus E1 and E2 proteins
Stephen Schuck1, Cristian Ruse, Arne Stenlund
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Journal of Virology
|May 3, 2013
Summary
Protein kinase CK2 phosphorylation regulates bovine papillomavirus E1 and E2 protein DNA binding. This phosphorylation controls viral replication, with E2 acting as a negative regulator during latent replication.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Papillomavirus life cycles are complex and not fully understood.
- Viral E1 and E2 proteins are crucial for transcription and DNA replication.
- Regulation of E1 and E2 protein activity remains largely unclear.
Purpose of the Study:
- To investigate the role of protein kinase CK2 in regulating bovine papillomavirus (BPV) E1 and E2 protein functions.
- To determine how CK2 phosphorylation affects the DNA binding activities of BPV E1 and E2 proteins.
- To elucidate the impact of CK2-mediated phosphorylation on viral DNA replication.
Main Methods:
- Investigated the effect of CK2 phosphorylation on BPV E1 and E2 protein DNA binding.
- Analyzed phosphorylation sites in E1 and E2 proteins using mutational analysis.
- Assessed the impact of mutations on viral DNA replication during latent and vegetative phases.
Main Results:
- CK2 phosphorylation of BPV E1 and E2 proteins alters their DNA binding activity.
- Phosphorylation of BPV E1's N-terminal domain leads to loss of DNA binding, conserved in human papillomavirus (HPV) E1.
- CK2 phosphorylation of BPV E2's hinge region also reduces DNA binding; mutations here increase latent replication.
- N-terminal E1 phosphorylation sites are not essential for latent replication but may be for vegetative replication.
Conclusions:
- CK2 phosphorylation is a key regulatory mechanism for BPV E1 and E2 protein biochemical activities.
- CK2 phosphorylation of E2 acts as a negative regulator of viral DNA replication during latency.
- E1 N-terminal phosphorylation likely plays a role in vegetative replication, potentially reversed by caspase 3 cleavage.
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