![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
26MB |
| Item Type: | Article |
|---|---|
| Title: | Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis |
| Creators Name: | Bogdanow, B., Schmidt, M., Weisbach, H., Gruska, I., Vetter, B., Imami, K., Ostermann, E., Brune, W., Selbach, M., Hagemeier, C. and Wiebusch, L. |
| Abstract: | Herpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction partners of human herpesvirus (HHV) CHPKs. We find that CHPKs can target key regulators of transcription and replication. The interaction with Cyclin A and associated factors is identified as a signature of β-herpesvirus kinases. Cyclin A is recruited via RXL motifs that overlap with nuclear localization signals (NLS) in the non-catalytic N termini. This architecture is conserved in HHV6, HHV7 and rodent cytomegaloviruses. Cyclin A binding competes with NLS function, enabling dynamic changes in CHPK localization and substrate phosphorylation. The cytomegalovirus kinase M97 sequesters Cyclin A in the cytosol, which is essential for viral inhibition of cellular replication. Our data highlight a fine-tuned and physiologically important interplay between a cellular cyclin and viral kinases. |
| Keywords: | Cyclin A, Cytomegalovirus, DNA, DNA Replication, HEK293 Cells, Herpesviridae, Herpesviridae Infections, NIH 3T3 Cells, Nuclear Localization Signals, Phosphorylation, Protein Interaction Maps, Protein Kinases, Viral Proteins, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 4845 |
| Date: | 24 September 2020 |
| Official Publication: | https://doi.org/10.1038/s41467-020-18542-1 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
